J. Alexander Fraser

Impaired delayed but preserved immediate grasping in a neglect patient with parieto-occipital lesions

Patients with optic ataxia, a deficit in visually guided action, paradoxically improve when pantomiming an action towards memorized stimuli. Visual form agnosic patient D.F. shows the exact opposite pattern of results: although being able to grasp objects in real-time she loses grip scaling when grasping an object from memory. Here we explored the dissociation between immediate and delayed grasping in a patient (F.S.) who after a parietal-occipital stroke presented with severe left visual neglect, a loss of awareness of the contralesional side of space. Although F.S. had preserved grip scaling even in his neglected field, he was markedly impaired when asked to pretend to grasp a leftward object from memory. Critically, his deficit cannot be simply explained by the absence of continuous on-line visual feedback, as F.S. was also able to grasp leftward objects in real-time when vision was removed. We suggest that regions surrounding the parietal-occipital sulcus, typically damaged in patients with optic ataxia but spared in F.S., seem to be essential for real-time actions. On the other hand, our data indicates that regions in the ventral visual stream, damaged in D.F but intact in F.S., would appear to be necessary but not sufficient for memory-guided action.

Emergence of Primary CNS Lymphoma in a Patient with Findings of CLIPPERS

We report the case of a patient who had clinical, radiological, and neuropathological features initially suggestive of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) but who ultimately succumbed to autopsy-proven primary central nervous system lymphoma (PCNSL). This case emphasizes the need for close follow-up of patients who are suspected to have CLIPPERS, and the importance of maintaining a continued high index of suspicion for an alternative diagnosis, particularly when such patients develop steroid-resistance. CLIPPERS is a recently described inflammatory disease1-3 centred in the pons with common features including: (1) episodic brainstem symptoms responsive to corticosteroids and immunotherapy; (2) characteristic punctate and curvilinear gadolinium-enhancing lesions predominantly in the pons with variable involvement of other structures including the cerebellum, cerebral white matter, and spinal cord on magnetic resonance imaging (MRI); and (3) T-lymphocytic infiltrate with perivascular predominance in the brain biopsy specimens2. The original paper on CLIPPERS, by Pittock et al in 2010, described eight patients with common clinical, radiological, and pathological features. Since that time, two other case series2,3 described an additional 17 patients with similar features. Followup periods ranged from 6 to 408 months. It has been suggested that the combination of clinical and radiological features in CLIPPERS may be sufficiently distinctive that the disease could be diagnosed and treated without pathological examination, if alternative diagnoses are rigorously excluded1. However, making a definitive diagnosis remains challenging due to the lack of specific biomarkers and overlap in imaging features with a number of other disease entities, such as neurosarcoidosis, central nervous system (CNS) lymphoma, lymphomatoid granulomatosis, CNS vasculitis, chronic perivascular infectious process, Behçet disease, glioma, demyelinating disease, and histiocytosis1.

Plasma Exchange in a Patient with Tumefactive, Corticosteroid-Resistant Multiple Sclerosis.

Tumefactive multiple sclerosis (MS) is an aggressive form of MS that can be difficult to treat with standard therapies. In severe MS relapses, plasma exchange (PLEX) has shown some benefit, but reports of its use in patients with tumefactive MS are limited. This article describes the successful use of PLEX in a patient with tumefactive MS. A 46-year-old right-handed woman with a recent diagnosis of MS presented with drowsiness, dysarthria, horizontal nystagmus, and quadriparesis. Her brain magnetic resonance images demonstrated multiple tumefactive demyelinating lesions in the medulla, bilateral periventricular white matter, and corona radiata white matter. She was initially treated with a 10-day course of intravenous methylprednisolone without benefit; therefore, PLEX was initiated. After the second exchange, the patient started to improve and was discharged initially to rehabilitation and then home. She was started on disease-modifying therapy with natalizumab and did not experience further relapses but had slow clinical decline during the next year, which led to discontinuation of natalizumab treatment. PLEX may be used as second-line treatment in corticosteroid-resistant MS relapses, but there are limited reports of its use in patients with tumefactive MS. This patient presented with aggressive disease with multiple tumefactive lesions and did not respond to standard treatment with corticosteroids. PLEX was successful in improving her symptoms, allowing her to return home, although the disease progressed during the next year.

Predicting conversion to MS--the role of a history suggestive of demyelination.

BACKGROUND The ability to predict conversion to multiple sclerosis (MS) accurately when assessing a patient with a clinically isolated syndrome (CIS) is of paramount importance. Magnetic resonance imaging (MRI) is the best paraclinical tool currently available; however the significance of a history of an event suggestive of demyelination prior to CIS presentation has not been evaluated. METHODS A retrospective chart review of all optic neuritis cases presenting as CIS to a single neuro-ophthalmologist in London, Ontario between 1990 to 1998 was performed. Data were collected regarding demographics, past medical history, history of present illness, and family history. Conversion to MS was determined by the McDonald criteria after ten years of follow-up. Bayesian statistics and logistic regression were used to determine the best predictors of conversion to MS from CIS. RESULTS One hundred and sixteen optic neuritis subjects were included in the analysis. After ten years, 42.2% had converted to MS. The best predictor of future conversion remained at least one brain lesion, disseminated in space, on MRI (sensitivity 0.90, specificity 0.75). However, if the subject additionally had a history suggestive of a demyelinating event in the past that had not been confirmed clinically, the specificity increased to 0.96. These two traits taken together had an odds ratio of 27.8 for conversion to MS in the next ten years (p<0.001). CONCLUSIONS A history of an event suggestive of demyelination prior to presenting with optic neuritis as CIS increases the ability of the clinician to predict conversion to MS in the next ten years.

A selective impairment of perception of sound motion direction in peripheral space: A case study.

It is still an open question if the auditory system, similar to the visual system, processes auditory motion independently from other aspects of spatial hearing, such as static location. Here, we report psychophysical data from a patient (female, 42 and 44 years old at the time of two testing sessions), who suffered a bilateral occipital infarction over 12 years earlier, and who has extensive damage in the occipital lobe bilaterally, extending into inferior posterior temporal cortex bilaterally and into right parietal cortex. We measured the patients spatial hearing ability to discriminate static location, detect motion and perceive motion direction in both central (straight ahead), and right and left peripheral auditory space (50° to the left and right of straight ahead). Compared to control subjects, the patient was impaired in her perception of direction of auditory motion in peripheral auditory space, and the deficit was more pronounced on the right side. However, there was no impairment in her perception of the direction of auditory motion in central space. Furthermore, detection of motion and discrimination of static location were normal in both central and peripheral space. The patient also performed normally in a wide battery of non-spatial audiological tests. Our data are consistent with previous neuropsychological and neuroimaging results that link posterior temporal cortex and parietal cortex with the processing of auditory motion. Most importantly, however, our data break new ground by suggesting a division of auditory motion processing in terms of speed and direction and in terms of central and peripheral space.

Enzyme-inducing antiepileptic drugs and fractures in people with epilepsy: A systematic review

OBJECTIVE People with epilepsy (PWE) have an increased fracture risk, independent of seizures. Antiepileptic drugs are thought to increase this risk, particularly those that induce the hepatic cytochrome P450 enzyme system. We aimed to determine whether PWE treated with enzyme-inducing antiepileptic drugs (EIAEDs) have decreased bone mineral density (BMD), or increased fracture incidence, versus those treated with non-EIAEDs. METHODS We searched MedLine, EMBase, CENTRAL, and CINAHL prior to November 2014 for all studies comparing fracture risk, or BMD change, in PWE treated for ≥ 1 year with EIAEDs versus non-EIAEDs. RESULTS Thirteen observational studies met eligibility criteria. These studies, representing 68,973 adult PWE, were significantly heterogeneous, making meta-analysis impossible. Study results were split, with 5 studies showing decreased BMD in EIAED users, 5 studies showing no effect of EIAED on BMD, 2 studies showing increased fracture incidence in EIAED users, and 1 study showing no difference in fracture risk. The largest study (n = 63,259), which was also the most methodologically rigorous, showed an increased hazard ratio of 9-22% for any fracture, and 49-53% for hip fracture, in EIAED users. SIGNIFICANCE The literature is divided regarding the bone effects of EIAEDs; however, current best evidence supports an increased fracture risk in PWE treated with an EIAED compared to those treated with non-EIAEDs. A single article dominated our review, and other large methodologically rigorous studies are needed to confirm or refute its results. Further small studies, with limited power to control for multiple potentially confounding variables, are not likely to help.

Effect of Treating Acute Optic Neuritis With Bioequivalent Oral vs Intravenous Corticosteroids: A Randomized Clinical Trial

Importance Intravenous (IV) administration of corticosteroids is the standard of care in the treatment of acute optic neuritis. However, it is uncertain whether a bioequivalent dose of corticosteroid administered orally, which may be more cost-efficient and convenient for patients, is as effective as IV administration in the treatment of acute optic neuritis. Objective To determine whether recovery of vision following treatment of acute optic neuritis with a high-dose IV corticosteroid is superior to that with a bioequivalent dose of an oral corticosteroid. Design, Setting, and Participants This single-blind (participants unblinded) randomized clinical trial with 6-month follow-up was conducted at a single tertiary care center in London, Ontario, Canada. Participants were enrolled from March 2012 to May 2015, with the last participant’s final visit occurring November 2015. Patients 18 to 64 years of age presenting within 14 days of acute optic neuritis onset, without any recovery at time of randomization and without history of optic neuritis in the same eye, were screened. Inclusion criteria included best-corrected visual acuity (BCVA) of 20/40 or worse and corticosteroids deemed required by treating physician. In total, 89 participants were screened; 64 were eligible, but 9 declined to participate. Thus, 55 participants were enrolled and randomized. Primary analysis was unadjusted and according to the intention-to-treat principle. Interventions Participants were randomized 1:1 to the IV methylprednisolone sodium succinate (1000-mg) or oral prednisone (1250-mg) group. Main Outcomes and Measures Primary outcome was recovery of the latency of the P100 component of the visual evoked potential at 6 months. Secondary outcomes were the P100 latency at 1 month and BCVA as assessed with Early Treatment Diabetic Retinopathy Study letter scores on the alphabet chart and scores on low-contrast letters at 1 and 6 months. Results Of 55 randomized participants, the final analyzed cohort comprised 23 participants in the IV and 22 in the oral treatment groups. The mean (SD) age of the cohort was 34.6 (9.5) years, and there were 28 women (62.2%). At 6 months’ recovery, P100 latency in the IV group improved by 62.9 milliseconds (from a mean [SD] of 181.9 [53.6] to 119.0 [16.5] milliseconds), and the oral group improved by 66.7 milliseconds (from a mean [SD] of 200.5 [67.2] to 133.8 [31.5] milliseconds), with no significant difference between groups (P = .07). Similarly, no significant group difference was found in the mean P100 latency recovery at 1 month. For BCVA, recovery between the groups did not reach statistical significance at 1 month or 6 months. In addition, improvements in low-contrast (1.25% and 2.5%) BCVA were not significantly different between treatment groups at 1 or 6 months’ recovery. Conclusions and Relevance This study finds that bioequivalent doses of oral corticosteroids may be used as an alternative to IV corticosteroids to treat acute optic neuritis. Trial Registration clinicaltrials.gov Identifier: NCT01524250

Valsalva-triggered pseudotumor cerebri syndrome: Case series and pathogenetic implications

Objective To report the clinical and radiologic features of 3 patients in whom prolonged vigorous coughing/Valsalva triggered the development of pseudotumor cerebri syndrome (PTCS) that persisted even after the coughing attacks had stopped and to discuss how this novel proximate trigger supports a “hydraulic model” of PTCS pathogenesis. Methods This was a retrospective case series of 3 patients seen between January 2011 and July 2017 in a tertiary care neuro-ophthalmology clinic. Results Three female patients (ages 13, 28, and 21 years) were asymptomatic until developing prolonged fits of profuse coughing. Two patients had upper respiratory tract infections, and 1 patient had a prolonged asthma exacerbation. Symptoms typical of PTCS began 2 weeks into the coughing attacks, and patients were examined 1 to 2 weeks after coughing had ceased. One patient was overweight and 2 were obese. All 3 patients had papilledema, and 1 of 3 patients had lateral rectus palsy. Two of 3 patients had visual field defects, and all 3 patients had dural venous sinus stenoses (DVSS) on venous imaging. Lumbar puncture (LP) confirmed elevated opening pressures in 2 of 3 patients and brought immediate and sustained relief of symptoms; LP attempts failed in the third patient because of body habitus (body mass index 68 kg/m2). All patients were given acetazolamide and advised to work on weight loss. At follow-up 3 to 6 months later, all 3 patients had complete remission of their clinical syndromes and resolution of their DVSS on neuroimaging. Conclusions In susceptible individuals, prolonged coughing/Valsalva can trigger PTCS in the setting of collapsible (nonfixed) DVSS. This new observation supports a hydraulic model of PTCS pathogenesis.

Quantitative evaluation of vision-related and health-related quality of life after endoscopic transsphenoidal surgery for pituitary adenoma

OBJECTIVE Endoscopic resection of pituitary adenomas has been reported to improve vision function in up to 80%-90% of patients with visual impairment due to these adenomas. It is unclear how these reported rates translate into improvement in visual outcomes and general health as perceived by the patients. The authors evaluated self-assessed health-related quality of life (HR-QOL) and vision-related QOL (VR-QOL) in patients before and after endoscopic resection of pituitary adenomas. METHODS The authors prospectively collected data from 50 patients who underwent endoscopic resection of pituitary adenomas. This cohort included 32 patients (64%) with visual impairment preoperatively. Twenty-seven patients (54%) had pituitary dysfunction, including 17 (34%) with hormone-producing tumors. Patients completed the National Eye Institute Visual Functioning Questionnaire and the 36-Item Short Form Health Survey preoperatively and 6 weeks and 6 months after surgery. RESULTS Patients with preoperative visual impairment reported a significant impact of this condition on VR-QOL preoperatively, including general vision, near activities, and peripheral vision; they also noted vision-specific impacts on mental health, role difficulties, dependency, and driving. After endoscopic resection of adenomas, patients reported improvement across all these categories 6 weeks postoperatively, and this improvement was maintained by 6 months postoperatively. Patients with preoperative pituitary dysfunction, including hormone-producing tumors, perceived their general health and physical function as poorer, with some of these patients reporting improvement in perceived general health after the endoscopic surgery. All patients noted that their ability to work or perform activities of daily living was transiently reduced 6 weeks postoperatively, followed by significant improvement by 6 months after the surgery. CONCLUSIONS Both VR-QOL and patients perceptions of their ability to do work and perform other daily activities as a result of their physical health significantly improved by 6 months after endoscopic resection of pituitary adenoma. The use of multidimensional QOL questionnaires provides a precise assessment of perceived outcomes after endoscopic surgery.

Remission of nonparaneoplastic autoimmune retinopathy after minimal steroid treatment.

PURPOSE To describe the clinical findings in a patient demonstrating recovery from nonparaneoplastic autoimmune retinopathy after a minimal course of steroid treatment. METHODS Clinical presentation was documented, and paraclinical tests were obtained using Humphrey automated perimetry for visual fields, Western blotting for antiretinal antibodies, and electroretinography for evaluation of rod and cone function. RESULTS Initial presentation revealed marked visual field deficits, electroretinographic dysfunction, and the presence of α-enolase autoantibodies. After a brief course of oral corticosteroids, the patient demonstrated improvement in visual fields, disappearance of α-enolase autoantibodies, partial recovery of the cone on-response, and complete recovery of the rod response. CONCLUSION This case is distinguished from previous reports by the rapidity and degree of recovery, the brevity of treatment required, and the unique electroretinographic recovery pattern with concomitant disappearance of α-enolase autoantibodies. These findings suggest a pathologic role for α-enolase autoantibodies in autoimmune rod bipolar cell dysfunction. Identification of other cases exhibiting such improvements and associated autoantibody activity may expand our understanding of nonparaneoplastic autoimmune retinopathy disease pathogenesis.