Septo-optic dysplasia.

Septo-optic dysplasia is a rare disorder characterized by optic nerve hypoplasia; midline developmental defects including agenesis of the septum pellucidum, thinning or absence of the corpus callosum, or both; and deficiencies of pituitary hormones. The majority of cases are sporadic but rare familial cases occur. The clinical manifestations include poor visual function in one or both eyes, developmental delay, seizures, sleep disturbances, and precocious puberty. A life-long multidisciplinary approach is crucial in the management of these patients to optimize their growth and development and to help them lead as normal lives as possible.

Cerebrospinal fluid dynamics between the intracranial and the subarachnoid space of the optic nerve. Is it always bidirectional?

CSF is thought to flow continuously from the site of production in the ventricles into interconnected spaces; i.e. cisterns and subarachnoid spaces (SASs). Since the SAS of the optic nerve is defined by a cul-de-sac anatomy, it is not evident how local CSF might recycle from that region to the general SAS. The concept of free communication of CSF has recently been challenged by the description of a concentration gradient of beta-trace protein, a lipocalin-like prostaglandin d-synthase (L-PGDS), between the spinal CSF and that in the SAS of the optic nerve, indicating diminished local clearance or local overproduction of L-PGDS here. In fact, computed cisternography with a contrast agent in three patients with idiopathic intracranial hypertension and asymmetric papilloedema demonstrate a lack of contrast-loaded CSF in the SAS of the optic nerve despite it being present in the intracranial SAS, thus suggesting compartmentation of the SAS of the optic nerve. The concept of an optic nerve compartment syndrome is further supported by a concentration gradient of brain-derived L-PGDS between the spinal CSF and the CSF from the optic nerve SAS in the same patients.

Evaluating inter-fractional changes in volume and position during bladder radiotherapy and the effect of volume limitation as a method of reducing the internal margin of the planning target volume.

AIMS: To quantify the inter-fractional variation in bladder volume and position during a course of bladder radiotherapy, and to assess the feasibility of reducing the planning target volume (PTV) internal margin using an empty bladder protocol. MATERIALS AND METHODS: Weekly computed tomography scans were taken immediately after micturition on 15 patients undergoing radical radiotherapy for bladder cancer. Bladder volume and positional variation were compared by co-registration of the serial computed tomography scans with the initial planning scan and a single 'full' scan at the onset of treatment for each patient. A PTV was generated on the initial planning scan using both our departmental standard of 1.5cm and a reduced 1cm isotropic internal margin around the target (whole bladder) and the relative proportion of the bladder breaching the PTV using both margins compared. RESULTS: The mean post void residual volume from the planning scan was 112cm(3) (standard deviation 42cm(3)). The mean weekly variation in bladder volume relative to the planning volume was 0-12% (standard deviation 20-34%) with no observable trends over time. No statistically significant differences were seen in the proportion of bladder breaching the 1.5 and 1cm internal margin (P=0.18). Regression analysis showed that it is possible to ensure complete coverage of the bladder with a 1cm margin, providing the volume did not exceed over 50% of the initial planning scan volume. CONCLUSION: Using an empty bladder protocol and where on-line imaging is available it is feasible to reduce the internal margin of the PTV from 1.5 to 1cm, providing the volumes do not exceed >50% of the planning scan volume.

Carotid-cavernous fistula: current concepts in aetiology, investigation, and management.

A carotid-cavernous fistula (CCF) is an abnormal communication between arteries and veins within the cavernous sinus and may be classified as either direct or dural. Direct CCFs are characterized by a direct connection between the internal carotid artery (ICA) and the cavernous sinus, whereas dural CCFs result from an indirect connection involving cavernous arterial branches and the cavernous sinus. Direct CCFs frequently are traumatic in origin and also may be caused by rupture of an ICA aneurysm within the cavernous sinus, Ehlers-Danlos syndrome type IV, or iatrogenic intervention. Causes of dural CCFs include hypertension, fibromuscular dysplasia, Ehlers-Danlos type IV, and dissection of the ICA. Evaluation of a suspected CCF often involves non-invasive imaging techniques, including standard tonometry, pneumotonometry, ultrasound, computed tomographic scanning and angiography, and/or magnetic resonance imaging and angiography, but the gold standard for classification and diagnosis remains digital subtraction angiography. When a direct CCF is confirmed, first-line treatment is endovascular intervention, which may be accomplished using detachable balloons, coils, liquid embolic agents, or a combination of these tools. As dural CCFs often resolve spontaneously, low-risk cases may be managed conservatively. When invasive treatment is warranted, endovascular intervention or stereotactic radiosurgery may be performed. Modern endovascular techniques offer the ability to successfully treat CCFs with a low morbidity and virtually no mortality.

Isolated progressive visual loss after coiling of paraclinoid aneurysms.

BACKGROUND AND PURPOSE: The proximity of the paraclinoid segment of the internal carotid artery to the visual pathways may result in visual deficits when patients present with aneurysms in this segment. Although surgical clip ligation of these aneurysms has been the standard of care for decades, the advent of coil embolization has permitted endovascular therapy in those aneurysms with favorable dome-to-neck ratios. Although immediate nonprogressive visual loss after coil embolization of paraclinoid aneurysms has been well described, isolated progressive visual loss immediately or shortly following coil embolization, to our knowledge, has not. We have identified 8 patients who experienced progressive loss of vision, unassociated with any other neurologic deficits, developing immediately or shortly after apparently uncomplicated coil embolization of a paraclinoid aneurysm. MATERIALS AND METHODS: This study is a retrospective case series of 8 patients seen at 4 separate academic institutions. Inpatient and outpatient records were examined to determine patient demographics, previous ocular and medical history, and ophthalmic status before endovascular embolization. In addition, details of the primary endovascular therapy and subsequent surgical and nonsurgical interventions were recorded. Follow-up data, including most recent best-corrected visual acuity, postoperative course, and duration of follow-up were documented. RESULTS: Eight patients developed progressive visual loss in 1 or both eyes immediately or shortly after apparently uncomplicated coiling of a paraclinoid aneurysm. MR imaging findings suggested that the visual loss was most likely caused by perianeurysmal inflammation related to the coils used to embolize the aneurysm, enlargement or persistence of the aneurysm despite coiling, or a combination of these mechanisms. Most patients experienced improvement in vision, 2 apparently related to treatment with systemic corticosteroids. CONCLUSION: Patients in whom endovascular treatment of a paraclinoid aneurysm is contemplated should be warned about the potential for both isolated nonprogressive and progressive visual loss in 1 or both eyes. Patients in whom progressive visual loss occurs may benefit from treatment with systemic corticosteroids.

The optic nerve: a new window into cerebrospinal fluid composition?

Cerebrospinal fluid (CSF) pressure and composition are generally thought to be homogeneous within small limits throughout all CSF compartments. CSF sampled during lumbar puncture therefore should be representative for all CSF compartments. On the basis of clinical findings, histology and biochemical markers, we present for the first time strong evidence that the subarachnoid spaces (SAS) of the optic nerve (ON) can become separated from other CSF compartments in certain ON disorders, thus leading to an ON sheath compartment syndrome. This may result in an abnormal concentration gradient of CSF molecular markers determined in locally sampled CSF compared with CSF taken during lumbar puncture.

Differential modulation of gene induction by glucocorticoids and antiglucocorticoids in rat hepatoma tissue culture cells.

Studies of glucocorticoid and antiglucocorticoid induction of tyrosine aminotransferase (TAT) in two rat hepatoma cell lines (Fu5-5 and HTC) are described. These studies revealed several phenomena that are not consistent with the current models of steroid hormone action: (a) TAT induction occurred at glucocorticoid levels below those required for comparable receptor occupancy in Fu5-5, but not in HTC, cells; (b) the ability of antiglucocorticoids to induce TAT is higher in Fu5-5 than in HTC cells; (c) the values of the amount of TAT agonist activity with the antiglucocorticoid dexamethasone 21-mesylate and of log10 of the dexamethasone concentration required for half-maximal induction of TAT were not constant over time but varied in a linear, reciprocal manner. This modulation was seen for several glucocorticoids and antiglucocorticoids at the level of both TAT enzyme and mRNA but not for two other glucocorticoid inducible genes in the same cells. These results, plus the fact that a similar difference in the concentration required for half-maximal TAT induction in Fu5-5 cells was seen for both glucocorticoids and cyclic AMP, argue that the modulation occurs at some point distal to receptor-steroid complex binding to the biologically active nuclear sites but proximal to translation of TAT mRNA. In order to explain these results, it is pointed out that models involving second messengers are entirely appropriate for steroid hormone action. The participation of a modulated trans-acting factor in such a model may explain the above results.

Restricted expression of retrovirus nucleic acids and proteins in primate type C virus (gibbon ape leukemia virus-simian sarcoma virus)-initiated human B-lymphoblast cultures.

Fresh human B-lymphoblasts established in culture following exposure of adult peripheral blood leukocytes to type C retroviruses of the simian sarcoma virus/simian sarcoma-associated virus-gibbon ape leukemia virus group were analyzed in detail for the presence of the infecting virus. Viral expression ranged from production of low levels of intact virus in a few cultures to the presence of viral RNA and protein in the absence of detectable of levels of complete virus in the majority of the cultures. In situ molecular hybridization assays using 3H-labeled complementary DNA and indirect immunofluorescence assays using antibody to purified viral protein indicated that the expression of viral RNA and proteins are preferentially expressed in only a fraction of the cells in some cultures. If expression of the infecting viral sequences is necessary for the sustained growth of these cells, then those cells detectably synthesizing viral RNA and proteins may be influencing the growth of the remaining virus-negative cells. The lack of virus production in cultures synthesizing viral RNA and protein indicate that these human B-lymphocytes restrict the life cycle of these viruses at some step(s) after transcription of viral RNA or translation of viral protein.

Investigation of In Vivo skin stiffness anisotropy in breast cancer related lymphoedema.

There is a limited range of suitable measurement techniques for detecting and assessing breast cancer related lymphoedema (BCRL). This study investigated the suitability of using skin stiffness measurements, with a particular focus on the variation in stiffness with measurement direction (known as anisotropy). In addition to comparing affected tissue with the unaffected tissue on the corresponding site on the opposite limb, volunteers without BCRL were tested to establish the normal variability in stiffness anisotropy between these two corresponding regions of skin on each opposite limb. Multi-directional stiffness was measured with an Extensometer, within the higher stiffness region that skin typically displays at high applied strains, using a previously established protocol developed by the authors. Healthy volunteers showed no significant difference in anisotropy between regions of skin on opposite limbs (mean decrease of 4.7 +/-2.5% between non-dominant and dominant arms), whereas BCRL sufferers showed a significant difference between limbs (mean decrease of 51.0+/-16.3% between unaffected and affected arms). A large difference in anisotropy was apparent even for those with recent onset of the condition, indicating that the technique may have potential to be useful for early detection. This difference also appeared to increase with duration since onset. Therefore, measurement of stiffness anisotropy has potential value for the clinical assessment and diagnosis of skin conditions such as BCRL. The promising results justify a larger study with a larger number of participants.

Feasibility of using ultrasound for real-time tracking during radiotherapy.

This study was designed to examine the feasibility of utilizing transabdominal ultrasound for real-time monitoring of target motion during a radiotherapy fraction. A clinical Acuson 128/XP ultrasound scanner was used to image various stationary and moving phantoms while an Elekta SL25 linear accelerator radiotherapy treatment machine was operating. The ultrasound transducer was positioned to image from the outer edge of the treatment field at all times. Images were acquired to videotape and analyzed using in-house motion tracking algorithms to determine the effect of the SL25 on the quality of the displacement measurements. To determine the effect on the dosimetry of the presence of the transducer, dose distributions were examined using thermoluminescent dosimeters loaded into an Alderson Rando phantom and exposed to a 10 x 10 cm2 treatment field with and without the ultrasound transducer mounted 2.5 cm outside the field edge. The ultrasound images acquired a periodic noise that was shown to occur at the pulsing frequency of the treatment machine. Images of moving tissue were analyzed and the standard deviation on the displacement estimates within the tissue was identical with the SL25 on and off. This implies that the periodic noise did not significantly degrade the precision of the tracking algorithm (which was better than 0.01 mm). The presence of the transducer at the surface of the phantom presented only a 2.6% change to the dose distribution to the volume of the phantom. The feasibility of ultrasonic motion tracking during radiotherapy treatment is demonstrated. This presents the possibility of developing a noninvasive, real-time and low-cost method of tracking target motion during a treatment fraction.

Failure of penicillin G benzathine in the treatment of neurosyphilis.

Although penicillin remains highly effective in syphilis, important questions exist regarding the optimal regimen for syphilitic involvement of the nervous system. Progression of neurosyphilis despite 7.2 million units of penicillin G benzathine occurred in the case reported here, with subsequent resolution following high-dose intravenous aqueous penicillin therapy. This and other recent reports support the conclusion that neurosyphilis should be treated with higher amounts of penicillin than is provided by the benzathine regimens.

Current concepts in the diagnosis, pathogenesis and management of nonarteritic anterior ischaemic optic neuropathy.

Nonarteritic anterior ischaemic optic neuropathy (NAION) is the most common acute optic neuropathy in patients over the age of 50 and is the second most common cause of permanent optic nerve-related visual loss in adults after glaucoma. Patients typically present with acute, painless, unilateral loss of vision associated with a variable visual field defect, a relative afferent pupillary defect, a swollen, hyperaemic optic disc, and one or more flame-shaped peripapillary retinal haemorrhages. The pathogenesis of this condition is unknown, but it occurs primarily in patients with structurally small optic discs that have little or no cup and a variety of underlying vascular disorders that may or may not be known at the time of visual loss. There is no consistently beneficial medical or surgical treatment for the condition, but there are now animal models that allow testing of various potential therapies. About 40% of patients experience spontaneous improvement in visual acuity. Patients in whom NAION occurs in one eye have a 15-19% risk of developing a similar event in the opposite eye over the subsequent 5 years.

Preparation and EPR studies of lithium phthalocyanine radical as an oxymetric probe.

The electron paramagnetic resonance (EPR) spectrum of the paramagnetic center in solid lithium phthalocyanine, LiPc, exhibits a pO2 (partial pressure of oxygen)-dependent line width. The compound is insoluble in water and is not easily biodegradable and, therefore, is a useful spin probe for quantitative in vivo oxymetry. Because EPR spectrometry is potentially a useful technique to quantitatively obtain in vivo tissue pO2, such probes can be used to obtain physiological information. In this paper, a simple experimental procedure for the preparation of LiPc using potentiostatic electrochemical methods is described. The setup was relatively inexpensive and easy to implement. A constant potential ranging from 0.05 to 0.75 V versus Ag+/AgCl(s) was used for obtaining LiPc. The EPR spectral studies were carried out using spectrometers operating at X-band and at radiofrequency (RF) at different pO2 values to characterize the spectral response of these crystals. The results indicate that, depending on the electrolysis conditions, the products contain mixtures of crystals exhibiting pO2-sensitive and pO2-insensitive line widths. Electrolysis conditions are reported whereby the pO2-sensitive LiPc crystals were the predominant product. The influence of the working surface of the electrode and the electrolysis time on the yield were also evaluated. The crystals of LiPc were also studied using a time-domain RF EPR spectrometer. In time-domain EPR, the signals that survive beyond the spectrometer dead time are mainly the narrow lines corresponding to the pO2-sensitive crystals, whereas the signals arising from the pO2-insensitive component of LiPc were found not to survive beyond the spectrometer dead time. This signal survival makes the time-domain EPR method more sensitive for pO2 measurements using LiPc because the line width becomes very narrow at very low pO2 and, concomitantly, the relaxation time T2 longer, with no modulation or power saturation artifacts that are encountered as in the continuous wave (cw) mode. Further, minimal contributions from object motion in the spectral data obtained using time-domain methods make it an advantage for in vivo applications.

Monocular polyopia.

A patient with monocular polyopia underwent extensive neurologic investigation over a two-year period. Ocular examination disclosed a corneal degenerative change as the cause, and symptomatic relief was obtained with pilocarpine hydrochloride drops.

Does neuroretinitis rule out multiple sclerosis?

Neuroretinitis, a form of optic neuritis, is characterized by papillitis and a stellate macular exudate, or "macular star." The star implies the presence of a disc vasculopathy and secondary leakage of lipoproteinaceous material into the macula. Demyelinating optic neuritis would not be expected to produce a secondary macular exudate. We reviewed the literature on the risk of multiple sclerosis developing in a patient after an attack of optic neuritis, and rarely found a comment on the presence of a macular star. We then reviewed two series of 40 patients who had neuroretinitis and added ten patients of our own. Signs of multiple sclerosis had not developed in the 13 patients contacted retrospectively, nor in the patients followed up prospectively. We also noted that in our patients, neuroretinitis may be accompanied by other neurologic manifestations; neuroretinitis may be bilateral and may be staggered; papillitis may present without a macular star, only to have typical exudates develop up to two weeks later; and the macular exudate may take up to 12 months to resolve. We suggest that patients who demonstrate acute papillitis with a normal macula be reevaluated within two weeks for the development of a macular star. Its presence militates strongly against the subsequent development of multiple sclerosis.

Lumboperitoneal shunt for the treatment of pseudotumor cerebri.

We conducted a retrospective study of 27 patients with pseudotumor cerebri (PTC) treated with at least one lumboperitoneal shunt (LPS) to ascertain the efficacy of this treatment. The average duration of follow-up for this population was 77 months (median, 47 months), with a range of 21 to 278 months. A functioning LPS was successful in alleviating symptoms in all patients studied, and no patient with a functioning shunt complained of shunt-related symptoms, such as low-pressure headache or abdominal pain, within 2 months after the shunt was performed. Twelve patients (44%) required no revisions. The number of revisions among the 15 patients (56%) who required them ranged from 1 (5 patients) to 13 (1 patient). Three of these patients required 35 of the 66 total shunt revisions (53%). There were no major complications from LPS, other than failure of the shunt, even in patients who required multiple shunts. We conclude that placement of a lumboperitoneal shunt is satisfactory treatment for the majority of patients with PTC who require surgical therapy for the disorder, even though some patients ultimately require multiple shunt revisions.

Vigabatrin-associated retinal cone system dysfunction: electroretinogram and ophthalmologic findings.

OBJECTIVE: To determine the sources of vigabatrin-associated visual disturbances in patients treated for epilepsy. BACKGROUND: Vigabatrin is an extremely effective antiepileptic drug that selectively increases brain gamma-aminobutyric acid (GABA). Several patients recently developed constricted visual fields during vigabatrin treatment in the United Kingdom, indicating the possibility of GABA-associated retinal dysfunction. METHODS: Patients with visual symptoms treated chronically with vigabatrin at our center underwent visual evoked potentials (VEP), electroretinograms (ERG), and visual field and ophthalmologic examinations. RESULTS: Four of 38 patients treated with vigabatrin developed visual symptoms 2 to 40 months after starting the drug. Two patients complained of constricted visual fields and two had blurred vision. ERG demonstrated evidence of bilateral retinal dysfunction consistent with reduced inner retinal cone response in all four patients. Oscillatory potential responses were lost, suggesting impairment of the highly GABAergic amacrine cells. Two of the patients had normal VEPs and minimal findings on clinical ophthalmology examinations despite abnormal ERGs. Abnormal examination findings were narrowed retinal arteries, surface wrinkling retinopathy, and abnormal macular reflexes. One patient also had reduced rod photoreceptor function in the more symptomatic left eye. CONCLUSIONS: Visual field constriction and blurring during vigabatrin therapy is associated with retinal cone system dysfunction. Visual symptoms may represent selective vulnerability of retinas of affected patients to GABAergic effects of vigabatrin. The prevalence and course of retinal changes associated with vigabatrin therapy are important to determine in a larger group of patients.

Visual function loss from vigabatrin: effect of stopping the drug.

OBJECTIVE: To determine if visual function loss from vigabatrin use recovers after the drug is discontinued. BACKGROUND: Vigabatrin is an effective antiepileptic drug, but it is known to cause a variety of changes in visual function, including reductions in the visual field, visual acuity, color vision, and in electroretinogram (ERG) and electro-oculogram amplitudes. It is not known whether these changes are reversible. METHODS: Measurements of static and kinetic visual fields, visual acuity, color vision, and the ERG were recorded while patients were taking vigabatrin and again in 13 patients who had discontinued the drug because of lack of efficacy or reductions in visual field. Most of the patients had been off the drug for 3 to 6 months, although two patients had been drug-free for almost 1 year. RESULTS: Although ERG cone implicit time improved, most of the patients did not show improvement in either clinical measures of visual function (i.e., visual acuity, color vision, visual fields) or in ERG amplitudes. However, several patients who showed minimal visual field loss while on the drug had substantial recovery of ERG amplitudes. There was no statistical association between recovery of function and either duration of treatment or cumulative dosage. The multifocal ERG showed a diffuse loss of function that was not isolated to the periphery. CONCLUSIONS: Although the visual deficits in patients taking vigabatrin tend to be mild, most patients do not show improvement after they stop taking the drug. Visual field loss resulting from vigabatrin was not reversible. Visual acuity, color vision, and ERG amplitude loss may be reversible in patients with minimal or no field loss.

Visual dysfunction in patients receiving vigabatrin: clinical and electrophysiologic findings.

BACKGROUND: Vigabatrin is an antiepileptic drug that, although relatively well tolerated, is associated with visual field constriction and other visual disturbances of unclear origin. METHODS: We performed a complete neuroophthalmologic examination and electrophysiologic studies on 39 patients receiving vigabatrin and on 11 control patients. RESULTS: Nearly 50% of patients receiving vigabatrin had constricted visual fields compared with control patients. Some of the vigabatrin patients also had reduced visual acuity and abnormal color vision. In addition, most vigabatrin patients had abnormal electroretinographic results, the severity of which correlated strongly with the degree of visual field constriction. CONCLUSIONS: Vigabatrin can cause electrophysiologic evidence of retinal dysfunction and clinically detectable disturbances of visual sensory function.

Ocular pseudomyasthenia or ocular myasthenia 'plus': a warning to clinicians.

Myasthenia gravis (MG) commonly presents with weakness and fatigability of the lids and extraocular muscles, which respond to treatment with anticholinesterase medication. However, certain intracranial mass lesions may mimic these features of MG; alternatively, MG may mask the signs of a coexistent intracranial mass. We describe 8 patients originally diagnosed as having MG by knowledgeable clinicians, in whom an intracranial lesion instead of, or in addition to, MG was later identified. The lesions included parasellar tumors and aneurysms. In patients presenting with clinical features of ocular MG, it is therefore essential to establish a definite diagnosis of MG, to exclude other possible causes of "pseudomyasthenia," and to exclude other diseases that might be masked by coexisting myasthenic weakness. We recommend that patients with clinical features of MG limited to the ocular or cranial musculature be thoroughly evaluated for intracranial mass lesions, using CT or MRI if warranted.