Slower velocity perception with stronger optokinetic nystagmus: A paradoxical perception in virtual reality.

BACKGROUND: Optokinetic nystagmus (OKN) was studied in an immersive virtual reality (VR) environment with both typical optokinetic stimulation (OKs) wherein the head-tracking is active (similar to be sitting in front of a rotating drum) or a unique stimulus (VR-OKs) wherein the head-tracking is turned off, so head movements do not update the visual image (which moves with the head). OBJECTIVE: To study both the perception of the stimulus velocity and eye movements while subjects rotated their head from side to side and the visual scene was either a typical OKs or VR-OKs. METHODS: 9 healthy participants (aged 23 ± 2.4 y/o) had head and eye movements recorded under typical OKs and VR-OKS while smoothly rotating their head horizontally from side to side. Stimulation was delivered using a virtual reality setup on top of an eye movements recording system. RESULTS: Under VR-OKs participants perceived faster stimulus velocity when the head and stimulus had the same direction as compared to the head and stimulus in opposite directions. When the head turned in the same direction as the stimulus, there were fewer fast phase eye movements than when it rotated counter to stimulus motion direction. Conversely, with typical OKs, participants perceived faster stimulus velocity when the head and stimulus had opposite directions as compared to the head and stimulus having the same direction. CONCLUSIONS: The seemingly paradoxical results in which slower stimulus velocity is perceived in tandem with stronger nystagmus can be explained by the simultaneous activation of the Vestibulo-Ocular Reflex and OKN in accordance with the various visual and vestibular stimuli.

A pilot study of a novel specs for chronic dizziness.

OBJECTIVE: A pilot study to assess the efficacy and safety of a novel specs device developed to alleviate chronic dizziness using eyeglasses with referential marks fixed on the lenses. MATERIALS AND METHODS: Forty patients with stable symptoms of chronic dizziness for more than 3 months participated in a 4-week, double-blind, randomized treatment with Active-Specs or Sham-Specs. Efficacy was assessed using validated semiquantitative scales and questionnaires of vertigo, dizziness and anxiety. Safety evaluation included monitoring of any adverse event. RESULTS: Thirty-six participants were included in the efficacy analysis, 18 in each group. Twelve of 18 subjects (67%) treated with Active-Specs reported substantial improvement of symptoms compared to six (33%) with Sham-Specs showing a significant improvement on Clinical Global Impressions scale (P = .017). The Active-Specs group showed significant reduction in the Vertigo Visual Analogue Scale (P = .017) and a nonsignificant but consistent trend of improvement measured by the Dizziness Handicap Inventory and Beck Anxiety Inventory. There were no adverse events related to the treatment. CONCLUSIONS: This novel specs device seems to be a safe and promising novel treatment for chronic dizziness. We hypothesize that marks in specific zones of the peripheral visual field could strengthen information of real head motion counteracting the mismatch sensory and locomotor information causing chronic dizziness. The results of this pilot study should be followed up by additional studies aimed at confirming the present encouraging findings.

Vestibulo-ocular reflex dynamics with head-impulses discriminates spinocerebellar ataxias types 1, 2 and 3 and Friedreich ataxia.

OBJECTIVE: Although the diagnosis of inherited ataxias is ultimately genetic, this usually means an extensive and expensive process. This justifies the search for distinct clinical signs that may potentially help orient molecular diagnosis. METHODS: We explored the vestibulo-ocular reflex (VOR) with the video Head Impulse Test in patients diagnosed with spinocerebellar ataxia (SCA) type 3 (n = 15), type 1 (n = 4) and type 2 (n = 4), Friedreich's ataxia (FA) (n = 9) and healthy controls (n = 40). We estimated the latency, regression (VORr) and instantaneous VOR gain at 40, 60 and 80 ms (VOR40, VOR60 and VOR80), and determined the latency, peak-velocity and occurrence rate of catch-up saccades triggered with head-impulses. RESULTS: VOR latency was higher in FA (p < 0.001) and SCA3 (p = 0.02) as compared to controls, discriminating FA from other ataxic patients with an overall diagnostic accuracy of 88%. VORr, VOR40 and VOR60 were significantly lower in FA and SCA3 (p < 0.01). VOR80 was only significantly lower than controls in SCA3 (p < 0.01), discriminating these from other ataxic patients with an overall diagnostic accuracy of 78%. Covert saccades were only triggered in SCA3 but with low occurrence rate and peak velocity (11.1 ± 28.5% and 77.50 ± 15.30°/s) whereas overt saccades were present in all groups. VORr gain showed a negative correlation with disease severity evaluated with SARA (Spearman r = -0.46, p = 0.01). CONCLUSIONS: vHIT provides phenotypic information that differentiates these autosomal ataxias and can serve as a strategy to orient genetic diagnosis. A correlation between VOR and SARA raises the possibility of using VOR gain as a neurophysiologic biomarker for disease severity.

What is the true significance of donor-related cytomegalovirus transmission in the setting of facial composite tissue allotransplantation?

Face transplantation (FT) is fraught with complications parallel to solid organ transplantation (SOT). As such, donor-related cytomegalovirus (CMV) transmission remains one of the most commonly feared viruses associated with FT. With this in mind, a review of the literature seemed justified, knowing that two of the first four face transplant recipients acquired CMV donor-related viral infection. Although the risk of CMV transmission is acceptable in the setting of SOT, the scenario for those composite tissue allotransplantation (CTA) patients, who are often young and healthy, may be different. Experiences from France and Cleveland have both confirmed suboptimal events related to CMV transmission following transplantation. Therefore, using the information provided here, it is imperative that all FT teams remain aware of these potential risks. Furthermore, all patients pursuing facial CTA should be fully informed as to the risks of donor-related CMV transmission, understand the importance of prophylaxis, and be aware of alternative therapies required to prevent symptomatic disease.

Overview of guidelines for establishing a face transplant program: a work in progress.

Since 2005, nine face transplants have been performed in four countries: France, the United States (US), China and Spain. These encouraging short-term outcomes, with the longest survivor approaching 5 years, have led to an increased interest in establishing face transplant programs worldwide. Therefore, the purpose of this article is to facilitate the dissemination of relevant details as per our experience in an effort to assist those medical centers interested in establishing a face transplant program. In this article, we address the logistical challenges involved with face transplantation; including essential program requirements, protocol details, face transplant team assembly, project funding, the organ procurement organization and the coroner. It must be emphasized that face transplantation is still experimental and its therapeutic value remains to be validated. All surgical teams pursuing this endeavor must dedicate an attention to detail and should accept a responsibility to publish their outcomes in a transparent manner in order to contribute to the international field. However, due to its inherent complexity, facial transplantation should only be performed by university-affiliated medical institutions capable of orchestrating a specialized multidisciplinary team with a long-term commitment to its success.

Composite tissue allotransplantation: a proposed classification system based on relative complexity.

Numerous achievements have been made encompassing a wide array of composite tissue allograft (CTA) subtypes. We sought to develop a simple, reproducible CTA classification system for the purpose of comparing clinical investigation. Each CTA subtype differs in relative complexity and can therefore be theoretically classified based on its unique combination of multiple factors. Eight complexity factors (CFs) are hypothesized: anatomic detail, psychological obstacles, rejection risk, required rehabilitation, relative antigenicity, functionality/cosmesis, skin ratio, and salvageability. A distribution of total complexity scores, ranging from 8 to 24, is classified into 3 ordered categories representing varying degrees of complexity. In conclusion, we have created a new classification system so that ongoing research and future data may be compared in a type-specific fashion.

Benign paroxysmal positional vertigo as the cause of dizziness in patients after severe traumatic brain injury: diagnosis and treatment.

OBJECTIVES: To identify patients with benign paroxysmal positional vertigo (BPPV) among patients with severe traumatic brain injury (TBI) and to evaluate the effectiveness of the Particle Repositioning Maneouvre (PRM). DESIGN AND METHODS: Eighteen months prospective study of 150 consecutive patients with severe TBI referred to an in-patients rehabilitation department. INTERVENTIONS: A structured interview emphasizing the possible presence of vertigo followed by a detailed neuro-otological examination. Patients diagnosed with BPPV were immediately treated with the PRM. MAIN OUTCOMES AND RESULTS: BPPV diagnosis was based on a positive Dix-Hallpike positional test. PRM efficacy was determined by repeating the positional test 1 or 2 weeks after treatment. Twenty out of 150 (13.3%) patients complained about positional vertigo. The diagnosis of BPPV was confirmed in 10 patients. Signs and symptoms were completely relieved in six patients after a single PRM, while the other four patients needed repeated treatment for complete resolution of BPPV. CONCLUSIONS: About half of the patients with severe TBI who complain about positional vertigo suffer from BPPV. These patients can be efficiently treated by physical maneouvres improving the rehabilitation outcome.

The saccadic system more readily co-processes orthogonal than co-linear saccades.

Real-life visual tasks such as tracking jumping objects and scanning visual scenes often require a sequence of saccadic eye movements. The ability of the ocular motor system to parallel process saccades has been previously demonstrated. We recorded the monocular eye movements of five normal human subjects using the magnetic search coil technique in a double step paradigm. Initial target jumps were always purely horizontal or purely vertical. We were interested in the latency to onset of the second saccade as a function of direction in relation to the first saccade. When the inter stimulus interval (ISI) was 150 or 180 ms orthogonal second saccades were of significantly shorter latency than second co-linear saccades. When the ISI was 250 ms the latencies of orthogonal and co-linear second saccades were statistically indistinguishable. Based on these findings it is postulated that the ocular motor system can more readily co-process orthogonal than co-linear saccades.

Electro-oculographic measures in patients with chronic whiplash and healthy subjects: a comparative study.

BACKGROUND: Despite their high incidence, costs, and long lasting disability, whiplash associated disorders (WAD) lack an identifiable objective pathology that explains their acute or chronic symptoms. OBJECTIVE: In view of previous suggestions of a possible effect of neck torsion on several electro-oculography (EOG) parameters, the main objective of this study was to examine their applicability in differentiating patients from uninvolved subjects. METHODS: Smooth pursuit and saccadic eye movements were assessed in 26 patients with chronic WAD and 23 healthy subjects. All tests were executed in three neck positions: neutral and rotations to left and right. RESULTS: Neck torsion did not influence eye movement performance of either the WAD or healthy groups. However, compared with the healthy group, patients with WAD had significantly lower smooth pursuit velocity gain (SPVG) (p = 0.01) and prolonged saccadic latency (p = 0.001), irrespective of neck position. CONCLUSIONS: Despite scattered differences that reached significance, the electro-oculographic measures used in this study do not seem to offer a clinically relevant method for differentiating between patients with WAD and normal subjects.

Repeated vs single physical maneuver in benign paroxysmal positional vertigo.

OBJECTIVES: To evaluate the effectiveness and possible side effects of a single session of repeated particle repositioning maneuver (PRM) to treat posterior canal benign paroxysmal positional vertigo (BPPV) and the usefulness of post-treatment restrictions. MATERIALS AND METHODS: A total of 125 consecutive patients with idiopathic BPPV participated in the study. Fifty patients received a single session of repeated PRM only (group I). Results were compared with those of 50 patients with BPPV who received a single PRM (group IIb), and 25 patients who received a single PRM followed by the use of a neck collar and keeping the head upright for 48 h (group IIa). RESULTS: Forty-six patients (92%) of group I, 40 patients (80%) of group IIb, and 21 patients (84%) of group IIa were completely free of signs and symptoms when re-examined 1 week after treatment. Transient nausea and disequilibrium following treatment were reported equally in all subgroups and well tolerated. Nearly all patients of group IIa considered the post-treatment restrictions very inconvenient. CONCLUSIONS: A single session of repeated physical procedure seems to be clinically superior to one single maneuver and well tolerated. Additional post-treatment measurements are inconvenient and should be abandoned.

Vestibulo-ocular arreflexia in families with spinocerebellar ataxia type 3 (Machado-Joseph disease).

OBJECTIVE: To identify the presence of vestibulo-ocular arreflexia in patients with Machado-Joseph disease (MJD), which can easily be diagnosed at the bedside. METHODS: Seven patients with MJD from five unrelated families and 11 patients with sporadic or hereditary cerebellar ataxia other than MJD underwent a detailed neuro-otological and oculomotor examination. Six MJD and five non-MJD patients also underwent electro-oculographic recordings and caloric tests. RESULTS: Gaze evoked nystagmus, smooth pursuit, and saccade abnormalities were found in both MJD and non-MJD patients. However, in all seven MJD patients but in none of the non-MJD patients, sudden passively induced head thrust to both sides elicited pathological corrective catch-up saccades, indicating bilateral loss of the horizontal vestibulo-ocular reflex. This was further confirmed in six MJD patients who had absent vestibular response to both a standard caloric test and ice water ear irrigation. Nystagmus was induced by standard caloric irrigation in all non-MJD patients examined. There was no correlation between the loss of vestibular function and the severity of cerebellar impairment. CONCLUSIONS: The presence of vestibulo-ocular arreflexia, as measured by the head thrust test in a patient with dominant cerebellar ataxia, strongly suggests the diagnosis of MJD.

The effects of dimenhydrinate, cinnarizine and transdermal scopolamine on performance.

We assessed the influence of dimenhydrinate, cinnarizine and transdermal scopolamine on the ability to perform simulated naval crew tasks. The effect of single doses of dimenhydrinate, 100 mg, cinnarizine, 50 mg, and one transdermal scopolamine patch on psychomotor performance was evaluated using a double-blind, placebo-controlled, randomized, crossover design in three separate studies. A total of 60 young naval crew (20 for dimenhydrinate, 15 for cinnarizine and 25 for transdermal scopolamine) underwent a battery of computerized and paper and pencil performance tests, and filled out a questionnaire on side-effects and well-being self-assessment. Dimenhydrinate significantly impaired decision reaction time and auditory digit span. Most of the subjects who took dimenhydrinate also reported a subjective decrease in well-being and general performance abilities. Cinnarizine and transdermal scopolamine did not affect performance abilities. Cinnarizine was free of significant side-effects. Dry mouth was the only significant side-effect of transdermal scopolamine. These findings could be explained by the well-known sedative properties of dimenhydrinate and not by a specific effect on any particular cognitive or motor function. Our results suggest that dimenhydrinate, 100 mg, adversely affects psychomotor function, whereas single doses of cinnarizine, 50 mg, and transdermal scopolamine appear to be free of side-effects on performance and seem to be a preferable anti-seasickness drug for use by a naval crew.

Telomerase activity in mouse myeloid leukemic cells and in cells from normal hematopoietic systems.

The telomeric repeat amplification protocol (TRAP) assay was used to measure telomerase activity in radiation-induced mouse myeloid leukemic (ML) cells and in several populations of normal cells. A detectable level of telomerase activity was found in normal hematopoietic tissues, i.e., bone marrow (BM) cells, day 9 colony-forming unit spleen (CFU-S) colonies, peripheral blood (PB) lymphocytes, and spleen. The level of telomerase activity in normal BM cells was used as a background level. Nine of the 12 cases of ML had higher levels of activity than that of the normal BM cells and therefore they were scored as ML with positive telomerase. The other three cases were considered as ML with negative telomerase because the levels of the enzyme were equivalent to that of normal BM cells. The data indicate that cellular differentiation may suppress telomerase activity in mouse ML cells. In summary, the results suggest that the CBA/Ca mouse model should be a useful animal system for future studies on the assessment of telomerase activity in both malignant and normal hematopoietic cells.

Inner ear decompression sickness in sport compressed-air diving.

OBJECTIVE: We report our experience over the past 12 years with recreational diving-related inner ear decompression sickness (IEDCS). STUDY DESIGN: Retrospective, consecutive case series. METHODS: Twenty-four divers, representing 29 cases of IEDCS, are presented with regard to evaluation, treatment, and follow-up. RESULTS: These 29 cases represent 26% of the severe decompression sickness (DCS) cases treated in that period. The patient group includes 22 divers who had a single event of IEDCS, one diver who had two events, and one with five repeated episodes. The cause of injury in 23 cases (79%) was violation of the decompression schedule. The mean time from surfacing to appearance of symptoms was 47 +/- 65 minutes. In 83%, symptoms appeared within 1 hour of ascent, in 97% within 2 hours, and in only one diver after 5.5 hours. Ten divers (34%) had pure vestibular involvement, 4 (14%) had cochlear insult alone, and 15 (52%) had combined vestibulo-cochlear injury. Except for one patient who had central as well as peripheral vestibulo-cochlear DCS, all the remaining patients had end organ involvement only, as demonstrated by physical examination and laboratory test results. Fifteen (52%) had isolated IEDCS, whereas 14 had additional symptoms of DCS. Twenty-six cases were treated by hyperbaric oxygenation with supplementary daily hyperbaric sessions. Of the 25 cases with vestibular injury and the 19 with cochlear damage, only 7 (28%) and 6 (32%), respectively, made a full recovery, whereas the others remained with residual damage. Of the 17 treated within 6 hours of symptom appearance, 9 (53%) were cured, compared with one of the 9 treated later (P <.05). CONCLUSIONS: IEDCS related to compressed-air recreational diving is more common than previously thought, and might occur even when no decompression schedule violation took place. Prompt diagnosis leading to the early commencement of hyperbaric oxygen recompression therapy is the key to complete recovery of cochlear and vestibular function.

Exposure of hooded capuchin monkeys (Cebus apella cay) to a rabid bat at a zoological park.

On 27 May 1999, a big brown bat (Eptesicus fuscus) was discovered on an island exhibit at the Denver Zoo that contained a troop of 15 hooded capuchin monkeys (Cebus apella cay). The monkeys were attacking the bat when it was discovered. The bat was collected and humanely euthanatized without direct handling and submitted to the Colorado Department of Public Health and Environment Virology Laboratory for rabies evaluation. The monkeys had not been vaccinated against rabies virus. The next day, the laboratory confirmed that the bat was positive for rabies. The recommendations from the Colorado Department of Public Health and Environment and the Centers for Disease Control and Prevention were to euthanatize the monkeys or quarantine them and comply with the human nonvaccinated postexposure protocol. A 1-ml dose of a killed rabies vaccine was administered i.m. in the hip on each of days 2, 7, 12, 19, and 33 postexposure, and a single dose of human rabies immune globulin was administered i.m. 5 days postexposure. Blood was collected under anesthesia in order to evaluate the immune response after rabies vaccination from six monkeys 5 days postexposure, six monkeys 19 days postexposure (five of the six monkeys were the same monkeys bled 5 days postexposure), 15 monkeys 67 days postexposure, and 13 monkeys approximately 1 yr postexposure. All of the monkeys developed and maintained levels of rabies virus neutralizing antibody above 0.05 IU/ml by 67 days postexposure. Although a serologic titer of 0.05 IU/ml indicates an adequate human response after rabies vaccination, no similar information is available for nonhuman primates. To date, none of the monkeys has succumbed to rabies.

[Pitfalls in the diagnosis of benign paroxysmal positional vertigo].

Benign paroxysmal positional vertigo (BPPV) is a common but often unrecognized cause of treatable vertigo. Possible causes of misdiagnosis of BPPV were studied by review of the records of 191 patients referred to our neurology clinic; 36 were identified as having BPPV not previously diagnosed. On referral the patients carried the following diagnoses: unspecified dizziness/vertigo (33%), transient ischemic attacks (28%), cervicogenic vertigo (19%), psychogenic dizziness/vertigo (11%), and others (8%). The paroxysmal nature of the vertigo and position-precipitating factors were not spontaneously reported by 31%. Atypical, even bizarre, symptoms including dizzy sensations were reported by 19%, and neck pain and headache were cardinal symptoms that accompanied vertigo. The Dix-Hallpike maneuver, which is essential for the diagnosis of BPPV, was not performed in any of the patients prior to referral. 30 (83%) experienced complete resolution of signs and symptoms after the first physical treatment session. We conclude that non-paroxysmal, non-positional vertigo does not rule out BPPV. Atypical and even bizarre complaints of dizziness, as well as neck pain and headache could be cardinal symptoms of BPPV. The Dix-Hallpike maneuver is mandatory in those complaining of dizziness and vertigo.

Characterization of genetic instability in radiation- and benzene-induced murine acute leukemia.

This study, using the CBA/Ca mouse as a model, compares genetic lesions associated with radiation- and benzene-induced acute leukemias. Specific types of leukemia included in the analyses are radiation-induced acute myeloid leukemia (ML), and benzene-induced lymphoblastic leukemias, lymphomas, or mix-lineage leukemias. These leukemias have histopathological characteristics similar to those seen in human acute leukemias. G-band cytogenetic analysis showed that specific deletions involving regions D-E of one copy of mouse chromosome 2 [del(2)(D-E)] were frequently associated in both radiation- and benzene-induced acute leukemias. In addition, translocations of chr2(D-E) were also observed in some cases. These results suggest an important role of chr2 (D-E) deletions and translocations in the development of radiation- and benzene-induced murine acute leukemias. Fluorescence in situ hybridization with DNA probes specific for 2(D-E), constructed in our laboratory by means of chromosomal microdissection and PCR amplification, also demonstrate 2(D-E) deletions and/or translocations in these leukemic cells. Aneuploidy of chromosomes 3, 15, 16, and Y were also frequently detected in benzene-induced leukemic cells with or without lesions on chr2. These cytogenetic findings support the previous observations that metabolites of benzene lead to spindle-fiber disruption or abnormal cytokinesis in exposed animals. In summary, genetic instabilities observed in leukemic cells isolated from mice that had developed leukemia after exposure to radiation or benzene are syntenic with those frequently detected in patients with myelodysplastic syndrome, acute ML, and acute lymphoblastic leukemia. Thus, the CBA/Ca mouse has several characteristics that make it an excellent model for the study of radiation or benzene leukemogenesis in humans.