J. Gert van Dijk

Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome

Roy Freeman • Wouter Wieling • Felicia B. Axelrod • David G. Benditt • Eduardo Benarroch • Italo Biaggioni • William P. Cheshire • Thomas Chelimsky • Pietro Cortelli • Christopher H. Gibbons • David S. Goldstein • Roger Hainsworth • Max J. Hilz • Giris Jacob • Horacio Kaufmann • Jens Jordan • Lewis A. Lipsitz • Benjamin D. Levine • Phillip A. Low • Christopher Mathias • Satish R. Raj • David Robertson • Paola Sandroni • Irwin Schatz • Ron Schondorff • Julian M. Stewart • J. Gert van Dijk

Natural history of obstetric brachial plexus palsy: a systematic review

Obstetric brachial plexus palsy (OBPP) is caused by traction to the brachial plexus during labour.1,2 In the majority of cases delivery of the upper shoulder is blocked by the mother’s pubic symphysis (shoulder dystocia). If additional traction is applied to the child’s head, the angle between the neck and the shoulder is forcefully widened, overstretching the ipsilateral brachial plexus. The resulting traction injury may vary from neurapraxia or axonotmesis to neurotmesis and avulsion of rootlets from the spinal cord. Recently, the exact origin of OBPP was again a matter of debate.3 It was suggested that intrauterine maladaptation, not nerve traction, causes the plexopathy. The incidence of OBPP varies from 1.6 to 2.9 per 1000 births in prospective studies.4,5 The upper brachial plexus is most commonly affected, resulting in paresis of the shoulder and biceps muscles, as first described by Erb and Duchenne.6 Hand function is additionally impaired in approximately 15% of patients;4,7,8 isolated injury to the lower plexus (Déjèrine-Klumpke’s type) is rare.9 The extent of neural damage can only be assessed by evaluating recovery in the course of time because nerve lesions of different severity initially present with the same clinical features. Neurapraxia and axonotmesis eventually result in complete recovery. Neurotmesis and root avulsion, on the other hand, result in permanent loss of arm function, which may lead in time to the development of skeletal malformations, cosmetic deformities, behavioural problems, and socioeconomic limitations.10–14 At present, most authors advise surgical exploration of the brachial plexus if spontaneous recovery is considered insufficient at a preset age.15–17 Absence of biceps function at 3 months of age is regarded as the key indicator for surgical exploration by some authors.15,18 Others use a combined score of different movements to decide whether nerve surgery should be performed at 9 months.16 Ancillary testing, in particular electromyography, is not considered reliable enough for prognostication.19,20 Methods of repair include nerve grafting after resection of the neuroma and nerve transfer in the case of root avulsion.15,21–25 Results achieved by these surgical approaches are claimed to be superior to the outcome in conservatively treated patients with equally severe lesions.15,26–28 However, this comparison relies on historical controls;29 no randomized study has been performed.6,30 In this context, the true percentage of infants who do not recover from OBPP becomes important as these children might benefit from reconstructive surgery. Reliable data on the frequency and severity of functional deficits in the natural course of OBPP are a prerequisite for developing adequate treatment strategies. Furthermore, such data would provide parents of newborn infants with OBPP with realistic information on prognosis. The prognosis of OPBB is generally considered to be very good, with complete or almost complete spontaneous recovery in over 90% of patients.25,31–35 However, this view is based on a limited number of studies37 which are cited indiscriminately without considering the methodology used. In the present review we performed a systematic literature search38 to clarify the natural course of untreated OBPP. Ideally, a study on the natural course of OBPP should be a prospective analysis of a demographic population with sufficient followup and clear end-stage assessment. We applied four predefined criteria to assess the methodological quality of the available studies: study-design, population, duration of follow-up, and assessment of end-stage.39

A single night of partial sleep deprivation induces insulin resistance in multiple metabolic pathways in healthy subjects.

BACKGROUND Subsequent nights with partial sleep restriction result in impaired glucose tolerance, but the effects on insulin sensitivity have not been characterized. OBJECTIVE The aim of this study was to evaluate the effect of a single night of partial sleep restriction on parameters of insulin sensitivity. RESEARCH DESIGN AND METHODS Nine healthy subjects (five men, four women) were studied once after a night of normal sleep duration (sleep allowed from 2300 to 0730 h), and once after a night of 4 h of sleep (sleep allowed from 0100 to 0500 h). Sleep characteristics were assessed by polysomnography. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp studies (from 1130 to 1430 h) with infusion of [6,6-(2)H(2)]glucose. RESULTS Sleep duration was shorter in the night with sleep restriction than in the unrestricted night (226 +/- 11 vs. 454 +/- 9 min; P< 0.0001). Sleep restriction did not affect basal levels of glucose, nonesterified fatty acids, insulin, or endogenous glucose production. Sleep restriction resulted in increased endogenous glucose production during the hyperinsulinemic clamp study compared to the unrestricted night (4.4 +/- 0.3 vs. 3.6 +/- 0.2 micromol x kg lean body mass(-1) x min(-1); P = 0.017), indicating hepatic insulin resistance. In addition, sleep restriction decreased the glucose disposal rate during the clamp (32.5 +/- 3.6 vs. 40.7 +/- 5.1 micromol x kg lean body mass(-1) x min(-1); P = 0009), reflecting decreased peripheral insulin sensitivity. Accordingly, sleep restriction decreased the rate of glucose infusion by approximately 25% (P = 0.001). Sleep restriction increased plasma nonesterified fatty acid levels during the clamp study (68 +/- 5 vs. 57 +/- 4 micromol/liter; P = 0.005). CONCLUSIONS Partial sleep deprivation during only a single night induces insulin resistance in multiple metabolic pathways in healthy subjects. This physiological observation may be of relevance for variations in glucoregulation in patients with type 1 and type 2 diabetes.

Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome.

Roy Freeman • Wouter Wieling • Felicia B. Axelrod • David G. Benditt • Eduardo Benarroch • Italo Biaggioni • William P. Cheshire • Thomas Chelimsky • Pietro Cortelli • Christopher H. Gibbons • David S. Goldstein • Roger Hainsworth • Max J. Hilz • Giris Jacob • Horacio Kaufmann • Jens Jordan • Lewis A. Lipsitz • Benjamin D. Levine • Phillip A. Low • Christopher Mathias • Satish R. Raj • David Robertson • Paola Sandroni • Irwin Schatz • Ron Schondorff • Julian M. Stewart • J. Gert van Dijk

Pathophysiology of chorea and bradykinesia in Huntington's disease

This article reviews the neurophysiological abnormalities described in Huntingtons disease. Among the typical features of choreic movements are variable and random patterns of electromyographic (EMG) activity, including cocontraction of agonist and antagonist muscles. Studies of premotor potentials show that choreic movements are not preceded by a Bereitschaftspotential, therefore demonstrating that choreic movement is involuntary. Early cortical median‐nerve somatosensory‐evoked potentials have reduced amplitudes and the reduction correlates with reduced glucose consumption in the caudate nucleus. Long‐latency stretch reflexes evoked in the small hand muscles are depressed. These findings may reflect failed thalamocortical relay of sensory information. In Huntingtons disease, the R2 response of the blink reflex has prolonged latencies, diminished amplitudes, and greater habituation than normal. These abnormalities correlate with the severity of chorea in the face. Patients with Huntingtons disease perform simple voluntary movements more slowly than normal subjects and with an abnormal triphasic EMG pattern. Bradykinesia is also present during their performance of simultaneous and sequential movements. Eye movements show abnormalities similar to those seen in arm movements. In Huntingtons disease, arm movement execution is associated with reduced PET activation of cortical frontal areas. Studies using transcranial magnetic stimulation show that patients with Huntingtons disease have normal corticospinal conduction but some patients have a prolonged cortical silent period. Bradykinesia results from degeneration of the basal ganglia output to the supplementary motor areas concerned with the initiation and maintenance of sequential movements. The coexisting hyperkinetic and hypokinetic movement disorders in patients with Huntingtons disease probably reflect the involvement of direct and indirect pathways in the basal ganglia–thalamus–cortical motor circuit.

Evolution of Epilepsy and EEG Findings in Angelman Syndrome

Summary: Purpose: To evaluate the evolution of epileptic seizures and EEG features in a large group of patients with Angelman syndrome (AS).

Obstetric lesions of the brachial plexus.

The few studies on prognosis of obstetric lesions of the brachial plexus that are not hampered by selection bias or a short follow‐up suggest that functional impairment persists in 20–25% of cases, more than commonly thought. Electromyography (EMG), potentially useful for prognosis, is often considered of little value. Denervation in the first week of life has been interpreted as evidence of an antenatal lesion, but is the logical result of the short axonal length affected. EMG performed at close to the time of possible intervention (3 months) usually shows a discrepancy: motor unit potentials are seen in clinically paralyzed muscles. This can be explained in five ways: an overly pessimistic clinical examination; overestimation of EMG recruitment due to small muscle fibers; persistent fetal innervation; developmental apraxia; or misdirection, in which axons reach inappropriate muscles. Further research into the pathophysiology of obstetric lesions of the brachial plexus is needed to improve prognostication.

Interictal cortical hyperexcitability in migraine patients demonstrated with transcranial magnetic stimulation

Cortical excitability to magnetic stimulation was investigated interictally in 10 patients with migraine with aura, 10 with migraine without aura and in 10 healthy volunteers. Thresholds, latencies and amplitudes of the magnetic-evoked potentials (MEPs) were measured from threshold to 100% stimulus intensity in 10% steps. Compound motor action potentials (CMAPs) evoked with supramaximal electrical stimulation of the ulnar nerve were used to calculate MEP/CMAP amplitude ratios. Thresholds and latencies of MEPs did not differ between patients and controls. MEP/CMAP amplitude ratios were significantly increased at all intensities in patients with migraine with aura (RM-ANOVA, p < 0.01) and without aura (p < 0.05) compared with controls. In migraine patients, MEP amplitudes and MEP/CMAP amplitude ratios were positively related to the frequency of migraine attacks (Spearmans r = 0.47, p < 0.01 and r = 0.56, p < 0.002, respectively). MEP parameters were not related to the side of the headache nor the aura, in either type of migraine, implying that both hemispheres are equally involved in migraine. Migraine with aura and, to a lesser extent, migraine without aura, are associated with increased interictal cortical excitability.

Clinical Dutch-English Lambert-Eaton Myasthenic Syndrome (LEMS) Tumor Association Prediction Score Accurately Predicts Small-Cell Lung Cancer in the LEMS

PURPOSE Approximately one half of patients with Lambert-Eaton myasthenic syndrome (LEMS) have small-cell lung carcinomas (SCLC), aggressive tumors with poor prognosis. In view of its profound impact on therapy and survival, we developed and validated a score to identify the presence of SCLC early in the course of LEMS. PATIENTS AND METHODS We derived a prediction score for SCLC in LEMS in a nationwide cohort of 107 Dutch patients, and validated it in a similar cohort of 112 British patients. A Dutch-English LEMS Tumor Association Prediction (DELTA-P) score was developed based on multivariate logistic regression. RESULTS Age at onset, smoking behavior, weight loss, Karnofsky performance status, bulbar involvement, male sexual impotence, and the presence of Sry-like high-mobility group box protein 1 serum antibodies were independent predictors for SCLC in LEMS. A DELTA-P score was derived allocating 1 point for the presence of each of the following items at or within 3 months from onset: age at onset ≥ 50 years, smoking at diagnosis, weight loss ≥ 5%, bulbar involvement, erectile dysfunction, and Karnofsky performance status lower than 70. The area under the curve of the receiver operating curve was 94.4% in the derivation cohort and 94.6% in the validation set. A DELTA-P score of 0 or 1 corresponded to a 0% to 2.6% chance of SCLC, whereas scores of 4, 5, and 6 corresponded to chances of SCLC of 93.5%, 96.6%, and 100%, respectively. CONCLUSION The simple clinical DELTA-P score discriminated patients with LEMS with and without SCLC with high accuracy early in the course of LEMS.

A guide to disorders causing transient loss of consciousness: focus on syncope

Episodes of transient loss of consciousness (TLOC) events pose diagnostic difficulties, as the causes are diverse, carry vastly different risks, and span various specialties. An inconsistent terminology contributes to the confusion. Here, we present a classification scheme for TLOC, based on ongoing multidisciplinary efforts including those of the Task Force on Syncope of the European Society of Cardiology. We also discuss the pathophysiology of TLOC and the key clinical features that aid diagnosis. TLOC is defined as an apparent loss of consciousness with an abrupt onset, a short duration, and a spontaneous and complete recovery. Syncope is defined as TLOC due to cerebral hypoperfusion, and is divided into reflex syncope (synonymous with neurally mediated syncope), syncope due to orthostatic hypotension, and cardiac syncope (arrhythmic or associated with structural cardiac disease). The other major groups of TLOC are generalized epileptic seizures, functional TLOC (psychogenic TLOC mimicking either epilepsy or syncope), and a further group of miscellaneous disorders. The management of patients who experience TLOC requires the recognition of the defining features of each of the major groups, and cooperation between different clinical specialties.