Optic Nerve Degeneration and Reduced Contrast Sensitivity Due to Folic Acid Deficiency: A Behavioral and Electrophysiological Study in Rhesus Monkeys.

Purpose: The purpose of the research was to elucidate the role of folic acid (B9) deficiency in the development of nutritional optic neuritis and to characterize the neurophysiological consequences of optic nerve degeneration in the cortical visual system. Methods: A combined behavioral and electrophysiological approach was applied to study luminance contrast sensitivity in two macaque monkeys affected by nutritional optic neuritis and in two healthy monkeys for comparison. For one monkey, a follow-up approach was applied to compare visual performance before onset of optic neuropathy, during the disease, and after treatment. Results: Optic nerve degeneration developed as a consequence of insufficient dietary intake of folic acid in two exemplars of macaque monkeys. The degeneration resulted in markedly reduced luminance contrast sensitivity as assessed behaviorally. In one monkey, we also measured visual activity in response to varying contrast at the level of single neurons in the cortical visual system and found a striking reduction in contrast sensitivity, as well as a marked increase in the latency of neuronal responses. Prolonged daily folate supplementation resulted in a significant recovery of function. Conclusions: Folic acid deficiency per se can lead to the development of optic nerve degeneration in otherwise healthy adult animals. The optic nerve degeneration strongly affects contrast sensitivity and leads to a distinct reduction in the strength and velocity of the incoming signal to cortical visual areas of the macaque brain, without directly affecting excitability and functional properties of cortical neurons.

Sudomotor dysfunction in patients with optic neuritis.

OBJECTIVES: Optic neuritis (ON) is a frequent initial manifestation of multiple sclerosis (MS). Autonomic failure affecting the pupillary function is known to exist in ON patients, and patients with MS are known to have more widespread autonomic dysfunction. For example, sudomotor dysfunction is well known in MS. We carried out a study investigating sudomotor abnormalities in ON patients, and later followed these patients at risk of developing MS. METHODS: Firstly, sudomotor function was measured by sympathetic skin responses (SSRs) in 13 ON patients and in 22 healthy controls. Secondly, thermoregulatory sweating was measured by an evaporimeter after a heating stimulus in 13 ON patients and in 14 healthy control subjects. RESULTS: The SSR latencies to electrical stimuli in the ON patients were significantly prolonged in the upper and lower extremities (p = 0.013-0.002), indicating sudomotor dysfunction. No statistically significant thermoregulatory sweating dysfunction could be found in the ON patients compared to the controls. All ON patients underwent a follow-up (mean duration 12.5 years) during which eight ON patients (62%) converted to clinically definite MS. It seemed that SSRs had no value for identifying patients who later developed MS. INTERPRETATION: Our results enlarge the knowledge of autonomic disorders in ON patients, showing that sudomotor function may also be involved.

Normal levels of cerebrospinal fluid hypocretin-1 and daytime sleepiness during attacks of relapsing-remitting multiple sclerosis and monosymptomatic optic neuritis.

There is emerging evidence that multiple sclerosis (MS), the hypothalamic sleep-wake regulating neuropeptide hypocretin-1 (hcrt-1) and the sleep disorder narcolepsy may be connected. Thus, the major pathophysiological component of narcolepsy is lack of hcrt-1. Dysfunction of the hypocretin system has been reported in MS case reports with attacks of hypothalamic lesions, undetectable cerebrospinal fluid (CSF) hcrt-1 and hypersomnia, but not found during remission in small samples. Finally, daytime sleepiness, the major symptom of narcolepsy, is reported in several MS populations, and there are case reports of co-existent narcolepsy and MS. However, it is unknown whether hcrt-1 and daytime sleepiness generally change during MS attacks. We therefore analyzed whether daytime sleepiness (using the Epworth Sleepiness Scale (ESS)) and CSF hcrt-1 levels differed between MS attack and remission, in 48 consecutively referred patients with relapsing-remitting MS (RRMS) or monosymptomatic optic neuritis (MON). Twenty-seven patients were in attack and 21 in remission. ESS was normal both during attacks (5.4 +/- 3.0) and remission (5.8 +/- 2.6), and mean CSF hcrt-1 was normal (456 +/- 41 pg/ml). No statistically significant differences were found between attack and remission. MRI scans revealed no hypothalamic lesions. The results show that the hypocretin system is intact and sleepiness is not typical in RRMS and MON without hypothalamic lesions on MRI.

Comparative evaluation of megadose methylprednisolone with dexamethasone for treatment of primary typical optic neuritis.

AIM: To compare the efficacy of intravenous methylprednisolone and intravenous dexamethasone on visual recovery and evaluate their side-effects for the treatment of optic neuritis. MATERIALS AND METHODS: Prospective, randomized case-controlled study including 21 patients of acute optic neuritis presenting within eight days of onset and with visual acuity less then 20/60 in the affected eye who were randomly divided into two groups. Group I received intravenous dexamethasone 200 mg once daily for three days and Group II received intravenous methylprednisolone 250 mg/six-hourly for three days followed by oral prednisolone for 11 days. Parameters tested were pupillary reactions, visual acuity, fundus findings, color vision, contrast sensitivity, Goldmann visual fields and biochemical investigations for all patients at presentation and follow-up. RESULTS: Both groups were age and sex-matched. LOGMAR visual acuity at presentation was 1.10 +/- 0.52 in Group I and 1.52 +/- 0.43 in Group II. On day 90 of steroid therapy, visual acuity improved to 0.28 +/- 0.33 in Group I and 0.36 +/- 0.41 in Group II ( P =0.59). At three months there was no statistically significant difference in the color vision, contrast sensitivity, stereoacuity, Goldman fields and the amplitude and latency of visually evoked response between the two groups. The concentration of vitamin C, glucose, sodium, potassium, urea and creatinine were within the reported normal limits. CONCLUSION: Intravenous dexamethasone is an effective treatment for optic neuritis. However, larger studies are required to establish it as a safe, inexpensive and effective modality for the treatment of optic neuritis.

[Irrigation therapy as a method of intensive care of ophthalmopathology in the posterior eye segment in children].

Presented in the paper are data of a comparative analysis of efficiency of different methods of administration of drugs in neuritis and partial atrophy of the optic nerve. New techniques of application and fixation of irrigation systems in the retrobulbar and Tenon's space are described. Experimental and clinical data proving advantages of the new method of administration of drugs by an automatic pulse doser in the treatment of inflammatory diseases of the optic nerve are represented. The use of such intensive intermittent technique of administration of drugs in Tenon's space performed at the preliminary stage before electrostimulation of the optic nerve made the procedure by far more effective and ensured better treatment results.

Methylprednisolone increases neuronal apoptosis during autoimmune CNS inflammation by inhibition of an endogenous neuroprotective pathway.

Optic neuritis is one of the most common clinical manifestations of multiple sclerosis (MS), a chronic inflammatory disease of the CNS. High-dosage methylprednisolone treatment has been established as the standard therapy of acute inflammation of the optic nerve (ON). The rationale for corticosteroid treatment lies in the antiinflammatory and immunosuppressive properties of these drugs, as shown in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. To investigate the influence of methylprednisolone therapy on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the ON, we used a rat model of myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Optic neuritis was diagnosed by recording visual evoked potentials, and RGC function was monitored by measuring electroretinograms. Methylprednisolone treatment significantly increased RGC apoptosis during MOG-EAE. By Western blot analysis, we identified the underlying molecular mechanism: a suppression of mitogen-activated protein kinase (MAPK) phosphorylation, which is a key event in an endogenous neuroprotective pathway. The methylprednisolone-induced inhibition of MAPK phosphorylation was calcium dependent. Hence, we provide evidence for negative effects of steroid treatment on neuronal survival during chronic inflammatory autoimmune disease of the CNS, which should result in a reevaluation of the current therapy regimen.

Visual evoked potentials during hyperthermia.

OBJECTIVES: We sought to evaluate the effect of hyperthermia (HT) on central conduction pathways by alterations in pattern visual evoked potentials (PVEPs) in normal and demyelinated optic nerves. MATERIALS AND METHODS: We studied PVEP peak latency and amplitudes in 10 normal subjects and six patients with demyelinating optic neuropathy before and during HT. RESULTS: In normal subjects, a mean rise in temperature of 2.5 degrees C resulted in a decrease in the second positive peak (P2) latency of 6.1 ms (p < 0.0001) and a slight decline in P2 amplitude of 1.16 muV (p < 0.009). These results were compared to those obtained from six patients with multiple sclerosis. These patients had a history of monocular optic neuritis; two patients had had bilateral optic neuritis, and one patient had not had involvement of the optic nerve. Average temperature elevations during PVEPs were 1.60 degrees C. PVEPs among these patients showed decrease in mean P2 latencies, except in patients with multiple sclerosis, who showed an increase in latency with 60 min check size in the left eyes. There was a consistent decline in P2 amplitudes. Loss of amplitude was greater among the six optic nerves of those patients having transient, mild losses in visual acuity during HT. Reductions in P2 amplitude were best explained by partial or complete conduction block. CONCLUSIONS: These changes in conduction time and amplitude during HT provide a neurophysiologic correlation to the well-known sensitivity of demyelinated optic nerves to elevated temperatures. They are also relevant to the monitoring of central pathways in the operative or intensive care setting. The demonstrated reversible loss of amplitudes also gives promise to therapeutic manipulation of impaired pathways by impeding the loss of current from denuded nerve fibers.

Neuro-oftalmo-criptococosis en dos pacientes con SIDA / Neuro-ophthalmo-cryptococcosis in 2 patients with AIDS

La criptococosis es una causa importante de morbimortalidad en pacientes con Sida. Es la infección oportunística que ocurre en segundo lugar de frecuencia a nivel oftalmológico, después de la retinitis a citomegalovirus. Un 40 por ciento de los pacientes afectados de criptococosis meníngea presentan compromiso ocular. Se describen dos casos clínicos de compromiso neurooftalmológico con evolución fatal. Se analizan las manifestaciones clínicas, así como los exámenes diagnósticos pertinentes y aspectos terapéuticos

[Preliminary report on using general ozone therapy in diseases of the posterior segment of the eye]. / Wstepne doniesienie o stosowaniu ozonoterapii ogólnej w schorzeniach tylnego bieguna galki ocznej.

Autotransfusion of ozone venous blood was performed in 174 patients, in 32 patients ozone was given intraarterially. General ++ozone therapy was used for the first time in Poland in the following ophthalmological conditions: retinal pigment dystrophy, glaucomatous optic atrophy, in optic neuritis, after injuries and in cases of unknown aetiology; in degenerative-atrophic changes of the choroid, in high myopia, in post-inflammatory cases, in other degenerative diseases and in bacterial corneal ulcerations. Ozone therapy in these conditions seems to be favourable especially when the pathological process is not extensive. One could observe an improvement of the visual acuity and of the visual field.

Critical fusion frequency in MS during mild induced hyperthermia.

By raising the body temperature of 0.5 degrees C the critical fusion frequency of a flickering light increases in normal subjects but decreases in multiple sclerosis (MS) patients. The change was present in 14 patients with definite MS and in 5 of 10 patients with probable MS. No clinical worsening was observed during the procedure or in the following hours.

[Our experiences of PISCES (percutaneously inserted spinal cord electrical stimulation) in SMON and other neurologic disorders].

Percutaneously inserted spinal cord electrical stimulation (PISCES) was carried out in eleven intractable pain cases and in one spastic paraplegic case. The causes of intractable pain constitute subacute myelo-optic neuropathy (SMON) 6 cases, cerebrovascular disease 2 cases, multiple sclerosis (MS) 1 case, Charcot-Marie-Tooth (CMT) 1 case and transverse myelitis (TM) 1 case. The cause of spastic paraplegia was due to the ossification of posterior longitudinal ligament (OPLL). A trial stimulation was performed about two weeks before planning a permanent implantation of PISCES system. For the trial stimulation, epidural electrodes were percutaneously inserted with a guide of fluoroscopy in a X-ray room. The conditions of stimulation were adjusted to give an optimal electric dysesthesia. We employed pulse width 0.1-1.0 msec, pulse rate 1-120 Hz and pulse amplitude 0-10 Volt. If an excellent effect was obtained by trial study, we proceeded to the chronic implantation of PISCES system which were composed of epidural electrodes, a subcutaneous receiver and a surface antenna. The procedure of implantation was carried out in an operating room under local anesthesia. In our series, seven subjects (58%) experienced a rewarding effect by the trial stimulation and three underwent the permanent implantation of PISCES. We summarized the clinical courses of these three cases which were OPLL, CMT and SMON. Compared with the other methods for pain relief, PISCES is most characteristic in its safety and simplicity. To date, PISCES has been applied to various disorders; such as ataxia, spasticity, intractable pain, neurogenic bladder and peripheral vascular disease. But its efficacy has not been established in all these disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Auditory evoked phosphenes in optic nerve disease.

Five patients with optic neuropathy, four vascular and one demyelinating, are described who each complained of an unusual symptom. Bright flashes of light (phosphenes) occurred in the affected eyes and were evoked by sudden unexpected sounds. Movement of the eye alone did not reproduce the symptom. In all patients the phenomenon was sufficiently prominent to interfere with sleep and was the main complaint of one patient. An anticonvulsant (phenytoin) greatly reduced the frequency and intensity of the phosphene in one patient.