Rapid, non-contact multifocal visual assessment in multiple sclerosis.

OBJECTIVE: Previous work on temporally sparse multifocal methods suggests that the results are correlated with disability and progression in people with multiple sclerosis (PwMS). Here, we assess the diagnostic power of three cortically mediated sparse multifocal pupillographic objective perimetry (mfPOP) methods that quantified response-delay and light-sensitivity at up to 44 regions of both visual fields concurrently. METHODS: One high-spatial-resolution mfPOP method, P129, and two rapid medium-resolution methods, W12 and W20, were tested on 44 PwMS and controls. W12 and W20 took 82 s to test both visual fields concurrently, providing response delay and sensitivity at each field location, while P129 took 7 min. Diagnostic power was assessed using areas under the receiver operating characteristic (AUROC) curves and effect-size (Hedges' g). Linear models examined significance. Concurrent testing of both eyes permitted assessment of between-eye asymmetries. RESULTS: Per-region response delays and asymmetries achieved AUROCs of 86.6% ± 4.72% (mean ± SE) in relapsing-remitting MS, and 96.5% ± 2.30% in progressive MS. Performance increased with increasing disability scores, with even moderate EDSS 2 to 4.5 PwMS producing AUROCs of 82.1 to 89.8%, Hedge's g values up to 2.06, and p = 4.0e - 13. All tests performed well regardless of any history of optic neuritis. W12 and W20 performed as well or better than P129. CONCLUSION: Overall, the 82-s tests (W12 and W20) performed better than P129. The results suggest that mfPOP assesses a correlate of disease severity rather than a history of inflammation, and that it may be useful in the clinical management of PwMS.

A case report of a transient splenial lesion related to HaNDL syndrome.

BACKGROUND: Transient lesions in the splenium of the corpus callosum have been identified in many clinical cases, and often correspond to a metabolic insult to the brain. The syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL syndrome) is a rare but under-recognised headache syndrome. CASE: A 47-year-old man presented to our hospital with a 2-week history of intermittent headache, and acute right sided hemisensory deficit. A CSF lymphocytosis was found and a diagnosis of HaNDL was made. A lesion in the splenium of the corpus callosum was identified on MRI. CSF lymphocytosis and the splenial lesion resolved on follow up 4 weeks later. CONCLUSION: These two entities are uncommon but increasingly recognised. The co-incidence in this patient raises the possibility of similar underlying pathological mechanisms, including vasomotor changes in blood vessels, cortical spreading depression and glutamate excitotoxicity leading to intra-myelinic oedema. Awareness of these entities will allow prompt diagnosis, preventing unnecessary tests and treatment, and allow appropriate patient management.

Central control of eye movements.

PURPOSE OF REVIEW: Eye-movement research continues to provide an excellent tool for understanding the central control of motor function, both in health and disease. This article reviews recent findings in relation to saccadic eye movements, particularly antisaccades and microsaccades, with particular emphasis on the control of inaction, something which has recently become topical. RECENT FINDINGS: Microsaccades are under the control of the cerebral cortex, particularly the frontal and parietal eye fields. Their frequency and direction alters following presentation of visual stimuli. Spontaneous alterations in their frequency are correlated with alterations in the frequency of the gamma-band activity in the visual cortex as well as, interestingly, the heartbeat. Studies of saccades in Parkinson's disease have demonstrated abnormalities of prosaccade suppression which have variously been shown to correlate with freezing of gait, postural instability, minimal cognitive change and stimulation of the subthalamic nuclei. In stroke patients, abnormal patterns of saccade activity are associated with poor performance on reaching studies when using the weak arm. SUMMARY: Eye-movement studies continue to provide new insights into the control of movement in general but have been particularly useful in investigating the process of suppressing unwanted movement.

Lithium Poisoning.

Lithium is a commonly prescribed treatment for bipolar affective disorder. However, treatment is complicated by lithium's narrow therapeutic index and the influence of kidney function, both of which increase the risk of toxicity. Therefore, careful attention to dosing, monitoring, and titration is required. The cause of lithium poisoning influences treatment and 3 patterns are described: acute, acute-on-chronic, and chronic. Chronic poisoning is the most common etiology, is usually unintentional, and results from lithium intake exceeding elimination. This is most commonly due to impaired kidney function caused by volume depletion from lithium-induced nephrogenic diabetes insipidus or intercurrent illnesses and is also drug-induced. Lithium poisoning can affect multiple organs; however, the primary site of toxicity is the central nervous system and clinical manifestations vary from asymptomatic supratherapeutic drug concentrations to clinical toxicity such as confusion, ataxia, or seizures. Lithium poisoning has a low mortality rate; however, chronic lithium poisoning can require a prolonged hospital length of stay from impaired mobility and cognition and associated nosocomial complications. Persistent neurological deficits, in particular cerebellar, are described and the incidence and risk factors for its development are poorly understood, but it appears to be uncommon in uncomplicated acute poisoning. Lithium is readily dialyzable, and rationale support extracorporeal treatments to reduce the risk or the duration of toxicity in high-risk exposures. There is disagreement in the literature regarding factors that define patients most likely to benefit from treatments that enhance lithium elimination, including specific plasma lithium concentration thresholds. In the case of extracorporeal treatments, there are observational data in its favor, without evidence from randomized controlled trials (none have been performed), which may lead to conservative practices and potentially unnecessary interventions in some circumstances. More data are required to define the risk-benefit of extracorporeal treatments and their use (modality, duration) in the management of lithium poisoning.

Objective perimetry and progression of multiple sclerosis.

Introduction: We re-examined the per-region response amplitudes and delays obtained from multifocal pupillographic objective perimetry (mfPOP) after 10 years in 44 persons living with multiple sclerosis (PwMS), both to examine which parts of the visual field had progressed in terms of response properties and to examine if the baseline data could predict the overall progression of disease. Methods: Expanded Disability Status Scale (EDSS) scores were assessed in 2009 and 2019. Both eyes of each participant were concurrently tested at 44 locations/eye on both occasions. Several measures of clinical progression were examined, using logistic regression to determine the odds of progression. Results: At the second examination the 44 PwMS (31 females) were aged 61.0 ± 12.2 y. Mean EDSS had not changed significantly (3.69 ± 1.23 in 2009, 3.81 ± 2.00 in 2019). mfPOP delay increased progressively from inferior to superior regions of the visual fields while amplitudes demonstrated a temporal to nasal gradient. The mean of the 3 most delayed visual field regions was correlated with progression of MS by 2019 (p = 0.023). Logistic regression indicated a significant association between delay and odds of progression (p = 0.045): an individual with 3 regions at least 1 SD (40 ms) slower than the mean in 2009 had 2.05× (±SE: 1.43× to 2.95×) the odds of progression by 2019. A 1 SD shorter delay was associated with 2.05× lower odds of progression. Amplitude changes were not predictive of progression. Significance: mfPOP may provide a rapid, convenient method of monitoring and predicting MS progression.

Intensive glycemic control has no impact on the risk of heart failure in type 2 diabetic patients: evidence from a 37,229 patient meta-analysis.

BACKGROUND: More intensive glycemic control reduces the risk of microvascular disease in patients with diabetes mellitus but has not been proven to reduce the risk of macrovascular events such as myocardial infarction and stroke. Poorer glycemic control, as indicated by glycated hemoglobin level concentration, is associated with an increased risk of heart failure (HF), but it is not known whether improved glycemic control reduces this risk. We conducted a meta-analysis of randomized controlled trials comparing strategies of more versus less intensive glucose-lowering that reported HF events. METHODS: Two investigators independently searched PubMed, the Cochrane CENTRAL register of controlled trials, metaRegister, pre-MEDLINE, and CINAHL from January 1970 to October 2010 for prospective controlled randomized trials comparing a more intensive glucose-lowering regimen to a standard regimen. The outcome of interest was HF-related events (both fatal and nonfatal). Odds ratios (ORs) were calculated from published data from relevant trials and pooled with a random-effects meta-analysis. RESULTS: A total of 37,229 patients from 8 randomized trials were included in the analysis. Follow-up ranged from 2.3 to 10.1 years, and the overall number of HF-related events was 1469 (55% in the intensive treatment arm). The mean difference in glycated hemoglobin level between patients given standard treatment and those allocated to a more intensive regimen was 0.9%. Overall, the risk of HF-related events did not differ significantly between intensive glycemic control and standard treatment (OR 1.20, 95% CI 0.96-1.48), but the effect estimate was highly heterogeneous (I(2) = 69%). At subgroup analysis, intensive glycemic control achieved with high thiazolidinediones use significantly increased HF risk (OR 1.33, 95% CI 1.02-1.72). CONCLUSIONS: More intensive glycemic control in patients with type 2 diabetes mellitus did not reduce the occurrence of HF events. Furthermore, intensive glycemic control with thiazolidinediones increased the risk of HF. These findings question a direct mechanistic link between hyperglycemia and HF.

Miller Fisher Syndrome Associated With Immunotherapy for Metastatic Melanoma.

Immunotherapy is a treatment strategy that has demonstrated survival benefit for metastatic melanoma. Ipilimumab and nivolumab are examples of immunotherapy, in which monoclonal antibodies antagonize cytotoxic T-lymphocyte-associated protein 4 and programmed death-ligand 1 receptors, respectively, resulting in upregulation of the host immune response to cancer cells. There is increasing recognition of immune-mediated adverse events associated with immune therapies in patients with cancer. We present a case report of a patient who developed Miller Fisher syndrome associated with these therapies for metastatic melanoma along with a discussion of its management.

Can the ischemic penumbra be identified on noncontrast CT of acute stroke?

BACKGROUND AND PURPOSE: Early ischemic changes on noncontrast CT in acute stroke include both hypoattenuation and brain swelling, which may have different pathophysiological significance. METHODS: Noncontrast CT and CT perfusion brain scans from patients with suspected acute stroke <6 hours after onset were reviewed. Five raters independently scored noncontrast CTs blind to clinical data using the Alberta Stroke Program Early CT Score (ASPECTS). Each ASPECTS region was scored as hypodense or swollen. A separate reviewer measured time to peak and cerebral blood volume in each ASPECTS region on CT perfusion. Time to peak and cerebral blood volume were compared for each region categorized as normal, hypodense, or isodense and swollen. RESULTS: Scans of 32 subjects a median 155 minutes after onset yielded 228 regions with both CT perfusion and noncontrast CT data. Isodense swelling was associated with significantly higher cerebral blood volume (P=0.016) and with penumbral perfusion (posttest:pretest likelihood ratio 1.44 [95% CI: 0.68 to 2.90]), whereas hypodensity was associated with more severe time to peak delay and with core perfusion (likelihood ratio 3.47 [95% CI: 1.87 to 6.34]). Neither isodense swelling nor hypodensity was sensitive for prediction of perfusion pattern, but appearances were highly specific (87.2% and 91.0% for penumbra and core, respectively). Intrarater agreement was good or excellent, but interrater agreement for both hypodensity and swelling was poor. CONCLUSIONS: Regions exhibiting hypoattenuation are likely to represent the infarct core, whereas regions that are isodense and swollen have increased cerebral blood volume and are more likely to signify penumbral perfusion. Although noncontrast CT is not sensitive for detection of core and penumbra, appearances are specific. Some information on tissue viability can therefore be obtained from noncontrast CT.