Dennis Cordato

Post-vaccination encephalomyelitis: Literature review and illustrative case

Abstract Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that is usually considered a monophasic disease. ADEM forms one of several categories of primary inflammatory demyelinating disorders of the central nervous system including multiple sclerosis, optic neuropathy, acute transverse myelitis, and neuromyelitis optica (Devic’s disease). Post-infectious and post-immunisation encephalomyelitis make up about three-quarters of cases, where the timing of a febrile event is associated with the onset of neurological disease. Post-vaccination ADEM has been associated with several vaccines such as rabies, diphtheria–tetanus–polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, hepatitis B, and the Hog vaccine. We review ADEM with particular emphasis on vaccination as the precipitating factor. We performed a literature search using Medline (1976–2007) with search terms including “ADEM”, “acute disseminated encephalomyelitis”, “encephalomyelitis”, “vaccination”, and “immunisation”. A patient presenting with bilateral optic neuropathies within 3 weeks of “inactivated” influenza vaccination followed by delayed onset of ADEM 3 months post-vaccination is described.

Delirium within Three Days of Stroke in a Cohort of Elderly Patients

OBJECTIVES: To evaluate the incidence of stroke, risk factors for stroke, and outcomes in elderly stroke patients with delirium.

Utility of magnetic resonance imaging in diagnosing ulnarneuropathy at the elbow

OBJECTIVE Magnetic resonance imaging (MRI) of the ulnar nerve is being increasingly employed in the diagnosis of ulnar neuropathy at the elbow (UNE). Our aims were to: (i) assess the sensitivity of MRI in diagnosing UNE, especially in cases where neurophysiologic studies were non-localizing, (ii) determine the spectrum of MRI abnormalities in patients presenting with symptoms and signs of ulnar neuropathy, (iii) assess whether MRI findings differ between grades of UNE severity, and (iv) to see if MRI findings give an input into the pathological mechanisms of UNE. METHODS Clinical, neurophysiologic, and radiologic (MRI) records were reviewed in 52 patients with symptoms and signs of ulnar neuropathy. Ulnar nerve MRI studies were assessed by an unblinded observer. RESULTS The sensitivity of MRI at diagnosing UNE was higher than conventional nerve conduction studies, 90 versus 65%, respectively. In patients with non-localizing neurophysiologic studies (n=19), MRI disclosed changes consistent with UNE in 16 (84%) cases. The most frequent MRI findings included a combination of high signal intensity and nerve enlargement (63%), followed by nerve compression (27%) and isolated high signal intensity (23%), and isolated nerve enlargement (2%). There was no significant difference between patients with localizing and non-localizing neurophysiologic testing. Lastly, there were no differences between different grades of UNE, suggesting that UNE may be a neurophysiologically heterogeneous disorder. CONCLUSIONS MRI studies proved to be more sensitive than conventional nerve conduction studies at diagnosing UNE. In addition, the MRI studies were highly sensitive in patients with non-localizing UNE. SIGNIFICANCE Our study shows that MRI of the ulnar nerve should be used in patients with clinical features of UNE especially in those with non-localizing neurophysiologic testing.

Stroke risk factor, pattern and outcome in patients with cancer

Objective –  To investigate risk factors, stroke pattern and outcome in stroke patients with cancer.

Postoperative seizure outcome in a series of 114 patients with supratentorial arteriovenous malformations

The incidence of de novo and ongoing postoperative seizures and factors implicated in an increased likelihood of seizures following supratentorial cerebral arteriovenous malformation (AVM) resection remain controversial. We investigated the frequency, severity and variables associated with postoperative seizures in 114 consecutive patients who underwent complete surgical excision of supratentorial AVMs at our institution. The minimal follow up period was 24 months. The incidence of seizures post-AVM surgery was 21% (less than half that found preoperatively). The incidence of postoperative seizures first manifesting >12 months post-AVM resection was 6.3%. A history of preoperative seizures was associated with an increased likelihood of multiple (> or =4) seizures >1 month post-AVM resection (chi2 = 4.38, P = 0.04). Poor functional neurological outcome at 12 months was also a risk factor for the development of > or =1 postoperative seizure using logistic regression analysis (P = 0.04, odds ratio 1.52, 95% CI 1.01-2.28). Cessation of AED therapy in all patients who remain seizure-free at 12 months post-AVM resection is appropriate due to a low risk of new seizure onset or seizure recurrence.

Stereoselective interaction of thiopentone enantiomers with the GABAA receptor

As pharmacokinetic differences between the thiopentone enantiomers seem insufficient to explain the ∼2 fold greater potency for CNS effects of (−)‐S‐ over (+)‐R‐thiopentone, this study was performed to determine any enantioselectivity of thiopentone at the GABAA receptor, the primary receptor for barbiturate hypnotic effects. Two electrode voltage clamp recording was performed on Xenopus laevis oocytes expressing human GABAA receptor subtype α1β2γ2 to determine relative differences in potentiation of the GABA response by rac‐, (+)‐R‐ and (−)‐S‐thiopentone, and rac‐pentobarbitone. Changes in the cellular environment pH and in GABA concentrations were also evaluated. With 3 μM GABA, the EC50 values were (−)‐S‐thiopentone (mean 26.0±s.e.mean 3.2 μM, n=9 cells) >rac‐thiopentone (35.9±4.2 μM, n=6, P=0.1) >(+)‐R‐thiopentone (52.5±5.0 μM, n=8, P<0.02) >rac‐pentobarbitone (97.0±11.2 μM, n=11, P<0.01). Adjustment of environment pH to 7.0 or 8.0 did not alter the EC50 values for (+)‐R‐ or (−)‐S‐thiopentone. Uninjected oocytes responded to >100 μM (−)‐S‐ and R‐thiopentone. This direct response was abolished by intracellular oocyte injection of 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N1,N1‐tetraacetic acid (BAPTA), a Ca2+ chelating agent. With BAPTA, the EC50 values were (−)‐S‐thiopentone (20.6±3.2 μM, n=8) <(+)‐R‐thiopentone (36.2±3.2 μM, n=9, P<0.005). (−)‐S‐thiopentone was found to be ∼2 fold more potent than (+)‐R‐thiopentone in the potentiation of GABA at GABAA receptors expressed on Xenopus oocytes. This is consistent with the differences in potency for CNS depressant effects found in vivo.

Prevalence of Parkinson's disease in Sydney

Objective –  To examine the prevalence of Parkinsons disease (PD) in Bankstown, Sydney, using the same methodology as a previous study in Randwick, Sydney, Australia (1998–1999).

Identifying the determinants of 1-year post-stroke outcomes in elderly patients

Objectives –  To examine 12‐month outcomes and develop predictive models for outcomes in elderly stroke patients.

Comprehensive stroke units: a review of comparative evidence and experience

Background Stroke unit care offers significant benefits in survival and dependency when compared to general medical ward. Most stroke units are either acute or rehabilitation, but comprehensive (combined acute and rehabilitation) model (comprehensive stroke unit) is less common. Aim To examine different levels of evidence of comprehensive stroke unit compared to other organized inpatient stroke care and share local experience of comprehensive stroke units. Methods Cochrane Library and Medline (1980 to December 2010) review of English language articles comparing stroke units to alternative forms of stroke care delivery, different types of stroke unit models, and differences in processes of care within different stroke unit models. Different levels of comparative evidence of comprehensive stroke units to other models of stroke units are collected. Results There are no randomized controlled trials directly comparing comprehensive stroke units to other stroke unit models (either acute or rehabilitation). Comprehensive stroke units are associated with reduced length of stay and greatest reduction in combined death and dependency in a meta-analysis study when compared to other stroke unit models. Comprehensive stroke units also have better length of stay and functional outcome when compared to acute or rehabilitation stroke unit models in a cross-sectional study, and better length of stay in a ‘before-and-after’ comparative study. Components of stroke unit care that improve outcome are multifactorial and most probably include early mobilization. A comprehensive stroke unit model has been successfully implemented in metropolitan and rural hospital settings. Conclusions Comprehensive stroke units are associated with reductions in length of stay and combined death and dependency and improved functional outcomes compared to other stroke unit models. A comprehensive stroke unit model is worth considering as the preferred model of stroke unit care in the planning and delivery of metropolitan and rural stroke services.

Pharmacokinetics of Thiopental Enantiomers during and following Prolonged High-dose Therapy

BACKGROUND Thiopental is used as a racemate; however, this is not generally recognized. During conditions of prolonged high-dose therapy, the pharmacokinetics of thiopental may become nonlinear, but whether this derives from one or both enantiomers has not been evaluated. The authors determined the pharmacokinetics of R- and S-thiopental and serum concentrations of R- and S-pentobarbital from prolonged high-dose infusion of thiopental for neuroprotection. METHODS Twenty patients received a mean thiopental dose of 41.2 g over a mean duration of 95 h. R- and S-thiopental enantiomer serum concentration-time data from 18 patients were fitted with two models: a linear one-compartment model with first-order output, and a nonlinear one-compartment model with Michaelis-Menten output. RESULTS Nonlinear models were preferred in 16 of 18 patients. Paired analysis indicated that steady state clearance (Clss) and volume of distribution (Vd) were higher for R-thiopental (0.108 vs. 0.096 l/min, P < 0.0001; and 313 vs. 273 l, P < 0.0005, respectively); maximal rate of metabolism (Vm) was higher for S- than for R-thiopental (1.01 vs. 0.86 mg x l(-1) x h(-1), P = 0.02); elimination half-lives did not differ (14.6 vs. 14.7 h, P = 0.8); unbound fractions (f(u)) of R- and S-thiopental were 0.20 and 0.18, respectively, P < 0.0001). The differences in mean Clss, Vd and Vm were not significant when adjusted by f(u). Plasma concentrations of R- and S-pentobarbital were relatively small and unlikely to be of clinical significance. CONCLUSION The pharmacokinetics of R- and S-thiopental became nonlinear at these doses. The pharmacokinetic differences between R- and S-thiopental, although small, were statistically significant and were influenced by the higher f(u) of R-thiopental.