Seronegative neuromyelitis optica presenting with life-threatening respiratory failure

Context: Dyspnea has rarely been reported as a presenting symptom in patients with neuromyelitis optica (NMO). We report an unusual case of NMO relapse presenting with rapidly progressive respiratory failure and briefly discuss the possible pathophysiological mechanisms of this potential life-threatening complication of NMO.

Findings: The 58-year-old woman with a history of bilateral optic neuritis presented to the emergency department with rapidly worsening dyspnea. Cervical spine magnetic resonance imaging showed extensive abnormal signal with involvement of the medulla oblongata.

Since in our patient chest radiography failed to disclose a diaphragmatic palsy that is commonly observed in patients with phrenic nerve involvement, this acute manifestation of the disease may be attributed to brainstem involvement instead of cervical myelitis.

Conclusion/clinical relevance: Clinicians should be aware of this atypical presentation of NMO, which needs to be promptly recognized and aggressively treated.     

Functional evaluation of central cholinergic circuits in patients with Parkinson’s disease and REM sleep behavior disorder: a TMS study

Central cholinergic dysfunction has been reported in patients with Parkinson?s disease (PD) and hallucinations by evaluating short latency afferent inhibition (SAI), a transcranial magnetic stimulation protocol which gives the possibility to test an inhibitory cholinergic circuit in the human brain. REM sleep behavior disorder (RBD) was also found to be associated with cognitive impairment in PD patients. The objective of the study was to assess the cholinergic function, as measured by SAI, in PD patients with RBD (PD-RBD) and PD patients without RBD (PD-nRBD). We applied the SAI technique in 10 PD-RBD patients, in 13 PD-nRBD patients and in 15 age-matched normal controls. All PD patients and control subjects also underwent a comprehensive battery of neuropsychological tests. Mean SAI was significantly reduced in PD-RBD patients when compared with PD-nRBD patients and controls. Neuropsychological examination showed mild cognitive impairment in 9 out of the 10 PD-RBD patients, and in 5 out of the 13 PD-nRBD. SAI values correlated positively with neuropsychological tests measuring episodic verbal memory, executive functions, visuoconstructional and visuoperceptual abilities. Similar to that previously reported in the idiopathic form of RBD, SAI abnormalities suggest a cholinergic dysfunction in PD patients who develop cognitive impairment, and present findings indicate that RBD is an important determinant of MCI in PD.     

Stance ataxia and delayed leg muscle responses to postural perturbations in cervical spondylotic myelopathy

OBJECTIVE: We studied balance control in patients with cervical spondylosis, on the hypothesis that ataxia and changes in postural responses occur concurrently as a consequence of structural problems in the cervical cord. Subjects and patients: Seventeen patients and 17 healthy subjects were recruited. Based on magnetic resonance imaging, the patients were divided into 2 groups, with (n=9) and without (n=8) signs of myelopathy. METHODS: Body sway was recorded under quiet stance on a force platform. Postural perturbations evoked early and late responses in soleus and tibialis anterior. RESULTS: Most patients showed increased body sway during stance, which was larger in cervical spondylosis with myelopathy than cervical spondylosis. Early postural responses in the soleus were not affected. Late responses in soleus and tibialis anterior were delayed in cervical spondylosis with myelopathy. Across all patients, latency of tibialis anterior late response was correlated with lower limb sensory impairment and amplitude of body sway. CONCLUSION: Abnormal transmission through the cervical cord of proprioceptive input to supraspinal centres and of descending commands to caudal cord levels are accountable for ataxia in cervical spondylosis with myelopathy. Stabilometry may be an economic and easy way in a clinical and rehabilitative setting to distinguish severe from mild forms of cervical spondylosis prior to physical treatment and to help the differential diagnosis from other diseases featuring similar signs.     

First clinical trials of a new heteropolymer technology agent in normal healthy volunteers and patients with systemic lupus erythematosus: safety and proof of principle of the antigen-heteropolymer ETI-104

BACKGROUND: The heteropolymer technology was developed to remove pathogens from the circulation. OBJECTIVES: To evaluate the safety and tolerability of a single administration and to establish proof of principle for ETI-104 in normal healthy volunteers (NHV) and patients with systemic lupus erythematosus (SLE) METHODS: The drug was given intravenously to 11 NHV and six patients with SLE. Over 28 days, vital signs were noted, a haematological and chemical analysis of blood and urine was carried out, and adverse events were recorded. CR1 receptor numbers, the ability of antigen based heteropolymers to bind to red blood cells (RBCs), and the clearance of high avidity and total anti-dsDNA antibodies were measured by Farr assays and FACS analysis. RESULTS: No safety measure differed significantly from normal in both groups; no drug related serious adverse events occurred. ETI-104 rapidly bound to RBCs in NHV and patients with SLE. Binding of the drug to RBCs of patients with SLE also caused a rapid reduction of circulating anti-dsDNA antibodies in the plasma 15 minutes after administration, with a maximum reduction of 55% (range 43-62). At 28 days statistically significant decreases were maintained in three patients, while in the other three the values had returned to baseline levels. CONCLUSION: These clinical trials established the safety and the proof of principle of the new immunoconjugate ETI-104. This provides the basis for further development of this technology for numerous indications-for example, therapeutic options for autoimmune diseases or viral and bacterial infections.     

Point-of-care testing versus standard practice for chlamydia: a new approach to assessing the public health effect of rapid testing and treatment at local level

BackgroundChlamydia trachomatis is the most commonly diagnosed bacterial sexually transmitted infection in Britain. Present standards specify treatment within 14 days of testing positive; point-of-care testing (POCT) can eliminate this delay and potentially reduce loss to follow-up; its greater convenience might increase testing. 90-min nucleic acid amplification tests are the best available POCTs for chlamydia, with alternatives under development. However, cost-effectiveness depends on cost-per-test, sensitivity and specificity, and the effect of POCT on transmission.MethodsWe developed a user-friendly web-based method, based on a transmission-dynamic model for chlamydia, to assess the epidemiological impact and cost-effectiveness of introducing POCT in different local settings. The model uses behavioural and prevalence data from the National Survey of Sexual Attitudes and Lifestyles, and Public Health England surveillance data; these data inform on local-level variation, which is represented by sampling parameter values from within their ranges of uncertainty and selecting parameter sets that reproduce local coverage and diagnosis rates. The user can select different local settings, and vary sensitivity and specificity for the tests, specify costs (fixed and unit costs, including staff time), and then assess the effect of introducing POCT in different clinical services by comparison with a situation with no POCT. In the model, presumptive treatment is represented, which we expect to be reduced with the introduction of POCT because test results would be rapidly available to guide treatment.FindingsChanges in numbers of infections and diagnoses occurring under different scenarios (including conventional testing) were estimated, with uncertainty ranges, allowing calculation of total costs, and cost per infection (and serious sequelae) averted, while accommodating the considerable variation in chlamydia testing coverage, positivity, and diagnosis rates. Potential changes in sexual behaviour between test and treatment could determine the relative contribution of increased treatment rates and reduced treatment delay to the reduction in prevalence as a consequence of POCT.InterpretationThe effect of POCT was dependent on both the test performance characteristics and the assumptions about the implementation of the test across local services. Exploration of many uncertainties surrounding chlamydia epidemiology and screening implementation is possible with this model. This method can complement local and national knowledge, and contribute to local-level management of chlamydia infection.FundingInnovate UK (Technology Strategy Board), UK Medical Research Council, and the National Institute for Health Research. The Electronic Self-Testing Instruments for Sexually Transmitted Infection (eSTI2) Consortium eSTI2 is Funded under the UKCRC Translational Infection Research (TIR) Initiative supported by the Medical Research Council (Grant Number G0901608) with contributions to the Grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, the Chief Scientist Office of the Scottish Government Health Directorates, and the Wellcome Trust     

Repetitive transcranial magnetic stimulation transiently reduces punding in Parkinson’s disease: a preliminary study

Amongst the impulse-control disorders (ICDs) associated with dopamine-replacement therapy in patients with Parkinson’s disease (PD) is a repetitive, complex, stereotyped behaviour called punding. Disruption of the reciprocal loops between the striatum and structures in the prefrontal cortex (PFC) following dopamine depletion may predispose patients with PD to these behavioural disorders. The purpose of the present study was to assess the effects of repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral PFC (DLPFC) on punding in PD. We used low-frequency (LF) rTMS in four PD patients presenting with punding. Punding was transiently reversed by LF-rTMS over the DLPFC without enhancing motor impairment. The effect was more sustained after right DLPFC rTMS. Therefore, LF-rTMS produced a transient beneficial effect in PD patients with punding, similar to that reported in PD patients with levodopa-induced dyskinesias. rTMS might have therapeutic potential for the treatment of punding and perhaps other ICDs in PD.     

Altered Motor Cortex Excitability to Magnetic Stimulation in Alcohol Withdrawal Syndrome

Background: Alcohol addiction is a complex brain disease caused by alterations in crucial neurotransmitter systems, including gamma‐aminobutyric acid (GABA) and glutamate. These disturbances could be revealed by changes in cortical excitability parameters, as assessed by transcranial magnetic stimulation (TMS). This study was aimed to further investigate the complex pathophysiology of alcohol withdrawal syndrome (AWS). Methods: Motor cortex excitability was examined in 13 subjects with AWS in a mild predelirial state, in 12 chronic alcoholics and in 15 age‐matched control subjects, using a range of TMS protocols. Central motor conduction time, resting and active motor threshold, duration of the cortical silent period, short latency intracortical inhibition (SICI), and intracortical facilitation (ICF) to paired TMS were examined. Results: Intracortical facilitation was significantly increased in the AWS patients when compared with the chronic alcoholics and the control subjects. The other TMS parameters did not differ significantly from the controls. Administration of a single oral dose of the glutamatergic antagonist riluzole in a subgroup of 8 patients significantly reduced ICF; motor threshold and SICI were not affected by riluzole. Conclusion: Transcranial magnetic stimulation shows a selective increase in intracortical facilitation after ethanol withdrawal. Our findings support the theory that altered glutamatergic receptor function plays an important role in the pathogenesis of human alcohol withdrawal. This study provides further physiological evidence that antiglutamatergic approaches represent an efficacious alternative for treating alcohol withdrawal symptoms.     

Prognostic role of sentinel lymph node biopsy in breast cancer

Sentinel lymph node biopsy was shown to be an accurate procedure in the study of axillary lymph nodes; it allowed a marked decrease in surgery-related morbidity of breast cancer and axillary dissection could be avoided. Other parameters as molecular markers, nuclear grading, patient age, tumor size, are not able to predict the axillary lymph node status and consequent local therapeutic approach similar to those provided by sentinel lymph node biopsy. The extent of sentinel lymph node metastatic involvement, the extracapsular spread, the size of primary tumor and peritumoral lymphatic/vascular infiltration are the four characteristics shown to be significant, if considered in association and not separately as predictors of the extent of axillary involvement in presence of a positive sentinel lymph node. However, so far, specific studies did not confirm concordant and reproducible results. Therefore, apart from controlled studies, axillary dissection is always required in presence of a metastatic sentinel lymph node.