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

BACKGROUND AND PURPOSE: 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. METHODS: Retinal nerve fiber layer thickness was measured using optical coherence tomography (OCT) in 96 relapsing-remitting MS (RR-MS) patients and 46 controls. MRI was obtained within ±3 months of OCT. RNFLT associations with MRI measures from diffusion tensor imaging and regional and tissue specific atrophy were assessed. RESULTS: In RR-MS, lower RNFLT was associated with lower white matter volume and lower whole brain volume. Lower RNFLT was associated with lower total deep gray matter volume and lower thalamus volume. Lower RNFLT was associated with greater mean diffusivity (MD) in normal appearing (NA) brain tissue and NA gray matter. Trends were found for lower RNFLT with greater MD in NA white matter and thalamus. RNFLT in controls was not associated with MD. CONCLUSIONS: Lower RNFLT is associated with microscopic tissue injury in NA regions of the brain and with neurodegeneration of the deep gray matter and thalamus in RR-MS.

Cholesterol affects retinal nerve fiber layer thickness in patients with multiple sclerosis with optic neuritis.

BACKGROUND AND PURPOSE: To evaluate the associations between retinal nerve fiber layer (RNFL) thickness and lipid profiles in multiple sclerosis (MS). METHODS: This study enrolled 136 patients with MS (n = 272 eyes; 108 females, 28 males, mean age: 46.7 ± 8.9 years); 45% had a history of optic neuritis (ON). Subjects received optical coherence tomography (OCT) testing to assess RNFL thickness and visual acuity testing with Snellen charts. A subset of 88 patients received pattern reversal visual-evoked potential (PRVEP) testing. Lipid profiles consisting of serum high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and total cholesterol (TC) levels were obtained within ± 6 months of OCT. Regression analyses were used to assess the associations between RNFL thickness and lipid profile variables. RESULTS: Low RNFL thickness (P = 0.008) and higher PRVEP latency (P = 0.017) were associated with high LDL cholesterol > 100 mg/dl status. Low RNFL thickness (P = 0.008) and higher PRVEP latency (P = 0.043) were associated with high HDL cholesterol levels. Low RNFL thickness was also associated with HDL cholesterol > 60 mg/dl status (P = 0.001) and with TC > 200 mg/dl status (P = 0.015). The probability of average RNFL thickness in the lowest tertile (≤ 33rd percentile) was associated with interactions between TC > 200 mg/dl status (P = 0.001, odds ratio = 7.5, 95% confidence interval = 2.7-21) with affected/unaffected by ON status. CONCLUSIONS: High cholesterol adversely affects RNFL thickness in patients with MS with ON.

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 microm(n = 30) versus 108 +/- 5 microm (n = 10) in OND controls. In children with multiple sclerosis, average RNFLT +/- SD was 99 +/- 14 microm in unaffected (n = 24) versus 83 +/- 12 micromin eyes affected by optic neuritis ("affected eyes") (n = 10). Average RNFLT in children with acute disseminated encephalomyelitis and transverse myelitis was 102 +/- 15 microm in unaffected (n = 18) versus 67 +/- 17 microm in affected eyes (n = 6). In children with optic neuritis (ON), average RNFLT +/- SD was 97 +/- 13 microm in unaffected (n = 5) versus 89 +/- 12 microm 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.

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.

Elevated concentration of intraocular cortisol obtained by sequential parabulbar injection in rabbit model.

BACKGROUND: Parabulbar injections of corticosteroids yield a high intraocular concentration, but the half-life is short. We determined the concentration of cortisol that might be obtained by sequential parabulbar infusions of hydrocortisone. MATERIALS AND METHODS: Single parabulbar injections of hydrocortisone sodium succinate were made in a rabbit model and the time of maximum concentration and half-life determined in the retina-choroid, vitreous, serum, and the tissues of the paired eye by radio-immune assay. Based upon the half-life, sequential injections were made at 3 hour intervals to obtain a steady concentration. RESULTS: The maximum concentration of cortisol in the ocular tissues occurred two hours after a single injection and was 98 times greater in the choroid-retina and 72 times greater in the optic nerve than in the paired eye and the serum. The half-life of cortisol was 15 minutes. Elevated levels could be sustained by sequential injections at 3 hour intervals. CONCLUSION: Sequential injections of hydrocortisone through a retained parabulbar catheter could make it possible to titrate and maintain a therapeutic level of cortisol in the eyes of patients with posterior uveitis or optic neuritis.

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 high-signal 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.

Abnormal vergence with upper brainstem infarcts: pseudoabducens palsy.

BACKGROUND: Infarcts of the rostral brainstem often cause vertical gaze palsies but may also produce inappropriate convergence that manifests as pseudoabducens palsy and convergence-retraction nystagmus (CRN). Although the substrate for vergence has been defined in the monkey as lying dorsal and lateral to the oculomotor nucleus, the human homologue is unknown. METHOD: - The authors reviewed the clinical features, ocular findings, and CT or MR lesions in seven patients with pseudoabducens palsy and "top-of-the-basilar" infarction. They reviewed the literature for infarcts causing pseudoabducens palsy or CRN with precise autopsy localization. The authors then mapped the location of the infarcts on anatomic templates. RESULTS: The smallest MR infarct produced an ipsilateral pseudoabducens palsy and CRN, and was located just rostral to the oculomotor nucleus, near the midbrain-diencephalic junction. Two patients with only contralateral pseudoabducens palsy had both subthalamic and thalamic infarction. Four patients with bilateral pseudoabducens palsy had larger infarcts involving the midbrain. All patients with pseudoabducens palsy had upgaze palsy. Two patients with CRN from the literature had small infarcts near the midbrain-diencephalic junction at autopsy. CONCLUSIONS: Lesions near the midbrain-diencephalic junction are important for the development of pseudoabducens palsy. Pseudoabducens palsy and CRN are probably both manifestations of abnormal vergence activity. Inhibitory descending pathways for convergence may pass through the thalamus and decussate in the subthalamic region.

Thrombocytosis in temporal arteritis rising platelet counts: a red flag for giant cell arteritis.

OBJECTIVES: To determine whether early recognition and detection of thrombocytosis in patients with giant cell arteritis can help secure an earlier diagnosis, and whether it can help differentiate cases of arteritic optic neuropathy from other forms of optic neuropathy. METHODS: Medical and ophthalmologic records from 1993 to 1998 of the authors' patients with biopsy-proven temporal arteritis versus the authors' patients with nonarteritic anterior ischemic optic neuropathy and idiopathic demyelinating optic neuritis were prospectively collected. Past and present blood analyses were collected, and platelet counts were compared between patients with giant cell arteritis and control populations. This was done to determine whether thrombocytosis could help with the diagnosis and differentiation of these different disease states. RESULTS: There was a significant difference in the frequency of thrombocytosis in patients with giant cell arteritis (13 out of 19 patients), with or without arteritic ischemic optic neuropathy, as compared with those with nonarteritic anterior ischemic optic neuropathy (zero out of 30 patients), idiopathic optic neuritis (zero out of 26 patients), and healthy age-matched controls (one out of 22 control subjects). This difference was especially helpful in patients whose sedimentation rates were within the normal range (adjusting for age). Also noted was the finding that the rise in the platelet counts was not acute, but rather it was a slow gradual increase for approximately 12 months before the onset of significant systemic or visual symptoms. CONCLUSION: Thrombocytosis should be considered an important marker in patients being referred for evaluation of ischemic optic neuropathy, diplopia, amaurosis fugax, headache, or even generalized malaise. Westegren sedimentation rates <50 mm/hr are often erroneously viewed as nondiagnostic or equivocal in the elderly and just followed. An over-the-phone review of patients' sedimentation rates, complete blood counts, and platelet counts can lead to expedited evaluation and treatment of patients who may be at high risk of visual loss from temporal arteritis. Thrombocytosis should lower a physician's threshold to acutely treat patients for possible arteritic ischemic optic neuropathy until the disease is definitely ruled out.

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

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%).

The treatment of periocular and facial pain with topical capsaicin.

This article describes the effects of topically applied capsaicin (a nociceptive substance-P suppressor) in patients with neuropathic periocular or facial pain. Peripheral neuropathic pain is a major cause of periocular or facial discomfort and usually follows injury to a subcutaneous peripheral nerve. Though the damage is local, the pain tends to radiate. We studied three patients who complained of a 2- to 30-year history of fluctuating pain in the periocular area. All three had an area of point tenderness that responded to the topical application of capsaicin cream.

Clinical course of a cohort in the Cuban epidemic optic and peripheral neuropathy.

Nearly 51,000 Cubans were afflicted during an outbreak of an optic neuropathy (ON) and peripheral neuropathy (PN) between 1991 and 1993. We re-examined 14 of 20 affected individuals 16 months after an initial evaluation. The optic features were painless symmetric vision loss with poor visual acuity, color vision loss, central or cecocentral scotoma, optic disc pallor, and nerve fiber layer drop-out. The neurologic symptoms included stocking-glove sensory changes, hearing loss, leg cramps, sensory ataxia, hyperactive or absent reflexes, and complaints of memory loss. Two of 11 ON probands tested harbored Leber's hereditary optic neuropathy (LHON)-associated mitochondrial DNA mutations. All patients had received multivitamin therapy. We performed comparisons using the paired two-tailed t test. On re-examination, 12 of 14 patients demonstrated improvement. One patient remained unchanged. One woman with the nt-3460 mtDNA mutation showed a decline in vision. In patients not harboring mtDNA mutations, overall visual acuity, color vision, and peripheral neuropathy manifestations improved significantly (p < 0.001 for each manifestation). Most of the patients with Cuban ON and PN improved on multivitamin therapy. The significance of the mtDNA mutations is unclear. In the 2 LHON patients, manifestation of the disease may have been precipitated by nutritional deficiency. Patients with poor recovery or further deterioration should be evaluated for other factors, including poor vitamin therapy compliance and alternative diagnoses.

Mitochondrial DNA mutations in an outbreak of optic neuropathy in Cuba.

Since October 1991, nearly 51,000 Cubans have been afflicted in an outbreak of optic and peripheral neuropathies. To begin an investigation of the possible role of mitochondrial DNA (mtDNA) mutations in the outbreak, we studied mtDNA from 14 affected and two unaffected Cubans for the 12 mutations associated with Leber's hereditary optic neuropathy. Eleven probands (12 patients) had optic neuropathy and two had peripheral neuropathy only. We also studied two unaffected relatives of one proband. We identified two mtDNA mutations, at nucleotides 11778 and 3460, in two of the 11 probands with optic neuropathy. Although this data set is too small to reach statistically valid conclusions, it does suggest that mtDNA mutations might be contributing to the outbreak of optic neuropathy in Cuba.

Ferrous intraocular foreign bodies and magnetic resonance imaging.

We placed various sized ferrous foreign bodies in and around the eye, sclera, and orbit in a rabbit model before performing magnetic resonance imaging studies. All foreign bodies were detected on plain x-rays. Only one of the largest fragments (3 x 1 x 1 mm) demonstrated movement on exposure to the magnetic field.