Norah S. Lincoff

MRI findings in Susac’s syndrome

Background: Susac syndrome (SS) is a self-limited syndrome, presumably autoimmune, consisting of a clinical triad of encephalopathy, branch retinal artery occlusions, and hearing loss. All three elements of the triad may not be present or recognized, and MR imaging is often necessary to establish the diagnosis. Objective: To determine the spectrum of abnormalities on MRI in SS. Methods: The authors reviewed the MR images of 27 previously unreported patients with the clinical SS triad, and 51 patients from published articles in which the MR images were depicted or reported. Results: All 27 patients had multifocal supratentorial white matter lesions including the corpus callosum. The deep gray nuclei (basal ganglia and thalamus) were involved in 19 (70%). Nineteen (70%) also had parenchymal enhancement and 9 (33%) had leptomeningeal enhancement. Of the 51 cases from the literature, at least 32 had callosal lesions. The authors could not determine the presence of callosal lesions in 18 of these patients, and only one was reported to have a normal MRI at the onset of encephalopathy. Conclusions: The MR scans in SS show a rather distinctive pattern of supratentorial white matter lesions that always involve the corpus callosum. There is often deep gray matter, posterior fossa involvement, and frequent parenchymal with occasional leptomeningeal enhancement. The central callosal lesions differ from those in demyelinating disease, and should support the diagnosis of SS in patients with at least two of the three features of the clinical triad.

Retinal nerve fiber layer thickness is associated with brain MRI outcomes in multiple sclerosis

Multiple sclerosis is characterized by the dual pathological processes of inflammation and neurodegeneration. Conventional MRI techniques are considered the best tools for assessing and monitoring lesion burden and inflammation but are limited in their ability to assess axonal loss. Optical coherence tomography (OCT) is a simple high-resolution technique that uses near infrared light to quantify the thickness of the retinal nerve fiber layer (RNFL), which contains only non-myelinated axons. RNFL thickness (RNFLT) was measured using OCT on thirty consecutive MS patients (60 eyes). Eighteen patients underwent quantitative MRI analysis including T1- and T2-lesion volumes (LV), normalized brain volume (NBV), normalized cortical, white and gray matter volumes (NCV, NWMV, and NGMV), and mean whole brain diffusivity (MD). There was a strong association between NBV and average RNFL thickness (p<0.001, partial rp=0.77). The T2-LV and NWMV were significantly associated with average RNFL thickness (p=0.002, partial rp= -0.76 and p=0.005, partial rp=0.68, respectively) and there were trends toward association with T1-LV (p=0.041) and NGMV (p=0.067). There was negative correlation between average RNFL thickness (average of both eyes) and disability as assessed by EDSS (p=0.02). The results support potential usefulness of OCT for MS patient monitoring and research applications.

Abnormal vergence with upper brainstem infarcts: pseudoabducens palsy.

To the Editor: We read with interest the article by Pullicino et al.1 on seven patients with pseudoabducens palsy. As all their patients showed an associated upgaze palsy, the authors emphasized the importance of a localization close to the riMLF for the production of pseudoabducens palsy. Regarding the role of the thalamus in vergence control, particularly in association with the production of esotropia, the authors argue that because localization in previous reports of “thalamic esotropia” was based only on axial scans without coronal views,2 it still remains to be established beyond doubt that a lesion restricted to the thalamus can produce esotropia or pseudoabducens palsy. While the article by Pullicino et al. was in press, we reported a patient with selective loss of vergence control, consistent with the clinical findings of bilateral pseudoabducens palsy.3 Unlike previous reports, upgaze palsy was absent in our patient and MRI showed a symmetric paramedian thalamic infarction without midbrain lesion, documented by axial and coronal images. Our findings clearly demonstrate that exclusive paramedian thalamic lesions can produce esotropia or the clinical symptoms of pseudoabducens palsy. Like Pullicino et al. we suggest that these symptoms are caused by interruption of inhibitory convergence pathways as they traverse the paramedian thalamus.

Retinal nerve fiber thickness in inflammatory demyelinating diseases of childhood onset

Purpose To evaluate retinal nerve fiber layer thickness (RNFLT) using optical coherence tomography (OCT) in children with acquired demyelinating diseases. Methods This is a cross-sectional study of patients seen between 2006–2008 at the Pediatric MS Center of the Jacobs Neurological Institute. Consensus definitions for pediatric demyelinating disease were followed. All children received OCT testing and assessment of visual acuity (VA) using Snellen and low contrast letter acuity (LCLA) charts. Results Thirty-eight children diagnosed with acquired demyelinating disease, 15 healthy controls, and five children with other neurological disorders (OND) were included. Average RNFLT in healthy controls was 107 ± 12 μm(n = 30) versus 108 ± 5 μm (n = 10) in OND controls. In children with multiple sclerosis, average RNFLT ± SD was 99 ± 14 μm in unaffected (n = 24) versus 83 ± 12 μmin eyes affected by optic neuritis (“affected eyes”) (n = 10). Average RNFLT in children with acute disseminated encephalomyelitis and transverse myelitis was 102 ± 15 μm in unaffected (n = 18) versus 67 ± 17 μm in affected eyes (n = 6). In children with optic neuritis (ON), average RNFLT ± SD was 97 ± 13 μm in unaffected (n = 5) versus 89 ± 12 μm in affected eyes (n = 9). Differences between children with demyelinating disease and controls and between ON and nonON eyes were statistically significant (P < 0.001). Bivariate correlations of RNFLT with LCLA (P = 0.002) and VA (P < 0.001) were significant. Conclusions OCT may be a valuable tool for the assessment and monitoring of anterior optic pathway dysfunction in children with demyelinating diseases.

Leber’s hereditary optic neuropathy mitochondrial DNA mutations in familial multiple sclerosis

Abstract Leber’s hereditary optic neuropathy (LHON) can be difficult to distinguish from optic neuritis due to multiple sclerosis (MS). For several decades an association of LHON and MS has been suspected, and within the past 7 years the LHON nucleotide (nt)-3460 and nt-11778 mtDNA mutations have been identified in several patients with MS-like phenotypes. To further study this association, we tested 42 index patients with clinically definite, familial MS for the LHON mtDNA mutations at nt-3460, nt-11778, and nt-14484. No patients had a pathogenic LHON mtDNA mutation; however, two MS patients with unilateral optic neuritis harbored the nt-15257 mtDNA polymorphism that was reported originally as a pathogenic LHON mutation. Several investigators have shown evidence that the nt-15257 mtDNA mutation is not primarily pathogenic. Therefore, we conclude that pathogenic LHON mtDNA mutations are absent or rare in unselected patients with familial, clinically definite MS (95% confidence intervals for each of the negative mutations 0–7.0%).

Neurological Basis for Eye Movements of the Blind

When normal subjects fix their eyes upon a stationary target, their gaze is not perfectly still, due to small movements that prevent visual fading. Visual loss is known to cause greater instability of gaze, but reported comparisons with normal subjects using reliable measurement techniques are few. We measured binocular gaze using the magnetic search coil technique during attempted fixation (monocular or binocular viewing) of 4 individuals with childhood-onset of monocular visual loss, 2 individuals with late-onset monocular visual loss due to age-related macular degeneration, 2 individuals with bilateral visual loss, and 20 healthy control subjects. We also measured saccades to visual or somatosensory cues. We tested the hypothesis that gaze instability following visual impairment is caused by loss of inputs that normally optimize the performance of the neural network (integrator), which ensures both monocular and conjugate gaze stability. During binocular viewing, patients with early-onset monocular loss of vision showed greater instability of vertical gaze in the eye with visual loss and, to a lesser extent, in the normal eye, compared with control subjects. These vertical eye drifts were much more disjunctive than upward saccades. In individuals with late monocular visual loss, gaze stability was more similar to control subjects. Bilateral visual loss caused eye drifts that were larger than following monocular visual loss or in control subjects. Accurate saccades could be made to somatosensory cues by an individual with acquired blindness, but voluntary saccades were absent in an individual with congenital blindness. We conclude that the neural gaze-stabilizing network, which contains neurons with both binocular and monocular discharge preferences, is under adaptive visual control. Whereas monocular visual loss causes disjunctive gaze instability, binocular blindness causes both disjunctive and conjugate gaze instability (drifts and nystagmus). Inputs that bypass this neural network, such as projections to motoneurons for upward saccades, remain conjugate.

Orbital involvement as the initial manifestation of sarcoidosis: magnetic resonance imaging findings.

A 74‐year‐old man had diplopia, painful right ophthalmoplegia, proptosis, conjunctival injection, and facial skin lesions. Magnetic resonance imaging (MRI) revealed infiltration of the right intraorbital adipose tissue. Lesions were mixed low‐ and highsignal on T2‐weighted images and enhanced on fat‐suppressed T1‐weighted postcontrast images. A skin biopsy revealed numerous noncaseating granulomas consistent with sarcoidosis. Treatment with corticosteroids and chlorambucil led to a full clinical recovery. Sarcoidosis should be considered in the evaluation of orbital pseudotumor in elderly patients, even if no systemic manifestations of sarcoidosis are present

Retinal nerve fiber layer thickness and thalamus pathology in multiple sclerosis patients

Visual impairments are frequent in multiple sclerosis (MS). Optic neuritis can directly reduce retinal nerve fiber layer (RNFL) thickness. Our objectives were to evaluate associations of the RNFL thickness (RNFLT) of MS patients with magnetic resonance imaging (MRI) measures of regional brain atrophy and tissue injury in the post‐chiasmatic deep gray matter (GM) section of the visual pathway.

Novel treatment for radiation optic neuropathy with intravenous bevacizumab.

Radiation optic neuropathy is a devastating form of vision loss that can occur months to years after radiation therapy for tumors and other lesions located in close proximity to the visual pathways. We present the case of a 24-year-old woman who underwent external beam radiation for treatment of a tectal pilocytic astrocytoma, and 5 years later she developed bilateral radiation optic neuropathy and radiation necrosis of the right temporal lobe. We opted to treat her with intravenous bevacizumab with 3 doses every 3 weeks, as well as dexamethasone and pentoxifylline. After the first infusion of bevacizumab, the patient noted improvement in vision and color vision, and a follow-up magnetic resonance imaging study showed that the previous enhancement of the optic nerves and chiasm was diminishing. Her vision improved dramatically and has remained stable over a 3-year period.

Toluene optic neurotoxicity: magnetic resonance imaging and pathologic features.

Toluene, a colorless liquid found in glues, paints, and industrial products, is lipid soluble and rapidly absorbed by the lipid-rich central nervous system. Prolonged exposure through occupation or purposeful inhalation may lead to neurologic abnormalities. Two men presented with multifocal central nervous system defects and bilateral optic neuropathy of unclear etiology. After numerous diagnostic tests, including brain magnetic resonance imaging, lumbar puncture, hematologic studies, and in one patient a brain biopsy, chronic inhalation of toluene was found to be the cause. Timely diagnosis is important because patients may experience improvement in neurologic and ocular manifestations with cessation of exposure, whereas continued inhalant abuse or exposure can result in permanent loss of neurologic function.