Christian Lueck

CSF OPENING PRESSURE: REFERENCE INTERVAL AND THE EFFECT OF BODY MASS INDEX

We prospectively recorded CSF opening pressure in 242 adults who had a lumbar puncture with concomitant measurement of weight and height. The 95% reference interval for lumbar CSF opening pressure was 10 to 25 cm CSF. Body mass index had a small but clinically insignificant influence on CSF opening pressure.

A new dominantly inherited pure cerebellar ataxia, SCA 30

Background: The spinocerebellar ataxias (SCAs) are clinically and genetically heterogeneous. Currently, 27 forms are known, with the causative gene identified in 16. Although the majority of dominant pedigrees worldwide have SCAs 1, 2, 3, 6 or 8, new SCAs continue to be delineated. We describe a new disorder: SCA 30. Methods: An Australian family of Anglo-Celtic ethnicity manifested a relatively pure, slowly evolving ataxia. Six affected and four unaffected members were personally examined in a standardised fashion. MRI and nerve conduction studies were performed in two. An autosomal genome-wide linkage study was undertaken, and an in silico analysis of potential candidate genes in the linkage region was performed. Results: The six affected members had a relatively pure, slowly evolving ataxia developing in mid to late life, with only minor pyramidal signs and no evidence of neuropathy. All had hypermetric saccades with normal vestibulo-ocular reflex gain. Only one displayed (slight) gaze-evoked nystagmus. MRI showed cerebellar atrophy with preservation of nodulus/uvula and brainstem. Linkage analysis excluded currently known SCAs and identified a logarithm (base 10) of odds score of 3.0 at chromosome 4q34.3–q35.1, distinct from all previously reported loci. In silico prioritisation identified the gene ODZ3 as the most likely contender. Conclusions: SCA 30 is a previously undescribed cause of (relatively) pure adult-onset autosomal dominant cerebellar ataxia. The responsible gene is yet to be determined, but ODZ3 is a plausible candidate.

Sparse multifocal stimuli for the detection of multiple sclerosis

We compared the diagnostic capabilities of contrast reversal and sparse pattern pulse stimulation for dichoptic multifocal visual evoked potentials (mfVEPs) measured in normal subjects and multiple sclerosis (MS) patients. Multifocal responses were obtained from 27 normal subjects and 50 relapsing‐remitting patients, 26 of whom had experienced optic neuritis (ON+). The patient groups were matched for length of disease and number of clinical attacks. Compared with the responses of normal subjects those of MS patients had significantly smaller response amplitudes, lower signal‐to‐noise ratios, more complex response waveforms, and longer response delays. The effects were larger for sparser stimuli. Sensitivities and specificities for the different stimulus types were estimated from receiver operator characteristic (ROC) plots. Bootstrap estimates of the accuracies of the ROCs for the most promising measure, the template delays, indicated the sparsest stimulus would deliver 92% sensitivity at a false‐positive rate of 0%. In contrast, at 92% sensitivity the conventional mfVEP stimulus misdiagnosed more than 20% of the normal population. The results were similar for patients with no history of ON (ON−). In performing well in patients with no history of ON, the sparse mfVEPs seem to measure progressive damage associated with axon and gray matter losses rather than damage associated with a history of serious inflammation. Ann Neurol 2005;57:904–913

A mechanical theory to account for bitemporal hemianopia from chiasmal compression

The association between bitemporal hemianopia and chiasmal compression is well recognized. The majority of chiasmal syndromes are caused by extrinsic compression from pituitary tumors, suprasellar meningiomas, craniopharyngiomas, and aneurysms. However, it is not clear why compressive lesions of the chiasm show a predilection for damage to nasal fibers with bitemporal hemianopia. Few experimental attempts at elucidating these mysteries have been reported and none has provided an adequate explanation. The authors postulate that the susceptibility of nasal fibers to preferential damage is explained by structural collapse theories as applied to crossing and noncrossing cylinders. By constructing a simplified mathematical model, the authors demonstrate that nasal fibers are subject to relatively greater pressures for any given external compressive force acting on the chiasm.

Validation of the flexible electrogoniometer for measuring thoracic kyphosis.

Study Design. Three experiments to validate the use of the flexible electrogoniometer (FEG) as a tool to measure thoracic kyphosis. Objective. To investigate the accuracy, test-retest reliability, and concurrent validity of the FEG as applied to the thoracic spine. Summary of Background Data. Thoracic kyphosis is commonly measured by the Cobb angle from lateral radiograph. Other less-invasive tools have been developed, but all yield only static measurements or are restricted to the laboratory. The FEG, which can record joint angles over time outside the laboratory, has been used to measure other joints but has not yet been validated for measurement of the thoracic spine. Methods. First, the FEG was bench-tested against a plurimeter for accuracy. Second, 12 subjects performed 7 functional activities 1 week apart to assess the test-retest reliability. Finally, to examine concurrent validity, 12 subjects underwent radiography in “upright” and “slumped” standing with the FEG attached to the skin over their thoracic spine. Three Cobb angles, which corresponded with the inner, mid, and outer margins, respectively, of the overlying FEG end blocks were compared with the FEG angles. Results. The correlation between the FEG and the plurimeter was excellent (r > 0.99, P < 0.0001), although some accuracy was lost at extremes of range. The mean correlation between the first and second measurements was very strong (intraclass correlation coefficient2,1 0.92, P < 0.0001; range, 0.89–0.95). The mid-Cobb angle showed the least absolute angular difference from, and was highly correlated with, the FEG angle (r = 0.81, P < 0.01). Conclusion. The FEG demonstrated excellent accuracy and test-retest reliability and correlated very well with the Cobb angle. The FEG measurement seemed to correspond most closely with the Cobb angle measured between the middle of the FEG end blocks.

Cerebrospinal fluid pressure in adults

Background: Lumbar puncture (LP) is a widely-used investigative procedure. It allows relatively non-invasive measurement of intracranial pressure (ICP) which may have a significant impact on diagnosis and/or patient management. Over the years there has been considerable discussion about various aspects of the procedure, including what constitutes a normal opening pressure, what factors might influence this, and how LP is best performed. Evidence Acquisition: A review of the literature was carried out by searching PubMed and Medline, scanning relevant medical journals for recent publications, and carrying out secondary referencing and contacting other clinicians, where appropriate. Results: The normal range of ICP measured by LP in adults in a typical clinical setting should now be regarded as 6 to 25 cmH2O (95% confidence intervals), with a population mean of about 18 cmH2O. There is, however, considerable variability: some normal individuals have pressures of 30 cmH2O (or, occasionally, even higher) meaning that pressure measurements must be interpreted in the clinical context. Conclusions: This article aims to provide the practicing neuro-ophthalmologist with up-to-date information about the ways in which various factors can influence pressure measurements obtained at LP.

Reversible posterior encephalopathy syndrome associated with bortezomib

Reversible posterior encephalopathy (RPES) is an uncommon neurological syndrome that is being increasingly reported in association with anti‐neoplastic therapies. The first case of reversible posterior encephalopathy associated with the proteosome inhibitor bortezomib is described and the reported experience of the occurrence of RPES with other antineoplastic therapies reviewed. Dysregulation of cerebral vasomotor autoregulation is postulated as the underlying pathophysiology in this case of bortezomib associated RPES.

Sonographic differences in carpal tunnel syndrome with normal and abnormal nerve conduction studies.

We evaluated the differences in sonographic parameters in carpal tunnel syndrome (CTS) patients with normal and mildly abnormal nerve conduction studies (NCS). This was a prospective cross-sectional study. We assessed 169 wrists (101 patients) with a clinical diagnosis of carpal tunnel syndrome (CTS), as well as 20 healthy controls (40 wrists). 49 wrists were classified as mild NCS-positive and 38 as NCS-negative based on our laboratory NCS normal values. The cross-sectional area (CSA) of the median nerve at the carpal tunnel inlet and mid-forearm were measured and the wrist-to-forearm ratio (WFR) was calculated. 26% of the NCS-negative group had abnormal CSA. The CSA and WFR also differed significantly between the two groups. There was significant correlation between the sonographic and electrophysiologic variables. Ultrasound was diagnostic for CTS in a third of the NCS-negative wrists. Ultrasound may be useful in clinical CTS patients with normal or borderline NCS.

Assessment of point‐of‐care measurement of international normalised ratio using the CoaguChek XS Plus system in the setting of acute ischaemic stroke

Thrombolysis with alteplase (recombinant tissue plasminogen activator) is accepted hyperacute therapy for acute ischaemic stroke. Clotting must be normal before this can be administered safely. Laboratory testing of international normalised ratio (INR) takes 30–60 min, which can significantly delay administration of recombinant tissue plasminogen activator. Previous studies have suggested that point‐of‐care testing is useful in patients presenting with stroke and improves door‐to‐needle time. We performed a prospective study of point‐of‐care testing in patients presenting with acute ischaemic stroke.

Atrial fibrillation and anticoagulation in a stroke unit population.

Background:  Atrial fibrillation (AF) is an important predisposing factor for ischaemic stroke. There is evidence to suggest that even in appropriate candidates warfarin therapy is underutilized. We assessed the prevalence of AF in an Australian stroke unit to determine the degree of undertreatment at presentation.