[Driving status of syncope patients is not part of standard advice]. / Rijgeschiktheid bij syncope niet standaard besproken.

OBJECTIVE: Some medical problems, such as syncope, have direct consequences for fitness to drive. Our objective was to discover if patients had been informed about their driving status after a syncopal episode by their physician, and if this advice was in line with current legislation. DESIGN: Cross-sectional study. METHOD: By means of a structured questionnaire, 150 patients referred to the syncope clinic at the Academic Medical Centre, Amsterdam, were asked about the advice they had received concerning their driving status during previous consultations with their general practitioner or specialists. A syncope expert then assessed the driving status of all patients in the light of the existing and new ruling. RESULTS: In 121 of the 150 patients (81%), a certain or highly-likely cause for their loss of consciousness was determined: 68 patients had reflex syncope, 25 patients orthostatic hypotension, 20 patients psychogenic pseudosyncope, three patients cardiac syncope, three patients had epilepsy and two patients another diagnosis. Seven patients had experienced an episode while driving. Only 26/150 patients (17%) reported that the consequences of their episodes for their driving status had been discussed with them at earlier consultations. If driving was discussed, in only 31% had the current Dutch legislation on driving been followed. Over a third (38%) of the patients felt they should no longer drive. CONCLUSION: Fewer than one in five patients reported that driving status was discussed by a physician after a syncope episode. If advice had been given, it was often not in line with current legislation.

[Unexplained loss of consciousness: the diagnosis is never based on one symptom]. / Onverklaarde wegrakingen: de diagnose berust nooit op één symptoom.

Patients with transient loss of consciousness are often seen by a variety of specialists. Even if typical signs occur, it can be difficult to identify specific causes. We discuss two patients with complex presentations. The first patient was diagnosed with sleep syncope, a relatively unknown type of reflex syncope. The prodromal symptoms of discomfort and the subsequent loss of consciousness occurred while the patient was in bed or got up to go to the toilet due to abdominal symptoms. The onset in supine position was misleading, since this is a well-known alarm symptom of a possible cardiac cause. The second patient had vasovagal syncope followed by a psychogenic pseudosyncope. This resulted in frequent loss of consciousness of long duration with typical and atypical triggers and uncommon syncopal signs, including eye closure. These conflicting symptoms can be a pitfall and clinical expertise is required to identify the type of syncope.

Local injection of autologous bone marrow cells to regenerate muscle in patients with traumatic brachial plexus injury: a pilot study.

OBJECTIVES: Traumatic brachial plexus injury causes severe functional impairment of the arm. Elbow flexion is often affected. Nerve surgery or tendon transfers provide the only means to obtain improved elbow flexion. Unfortunately, the functionality of the arm often remains insufficient. Stem cell therapy could potentially improve muscle strength and avoid muscle-tendon transfer. This pilot study assesses the safety and regenerative potential of autologous bone marrow-derived mononuclear cell injection in partially denervated biceps. METHODS: Nine brachial plexus patients with insufficient elbow flexion (i.e., partial denervation) received intramuscular escalating doses of autologous bone marrow-derived mononuclear cells, combined with tendon transfers. Effect parameters included biceps biopsies, motor unit analysis on needle electromyography and computerised muscle tomography, before and after cell therapy. RESULTS: No adverse effects in vital signs, bone marrow aspiration sites, injection sites, or surgical wound were seen. After cell therapy there was a 52% decrease in muscle fibrosis (p = 0.01), an 80% increase in myofibre diameter (p = 0.007), a 50% increase in satellite cells (p = 0.045) and an 83% increase in capillary-to-myofibre ratio (p < 0.001) was shown. CT analysis demonstrated a 48% decrease in mean muscle density (p = 0.009). Motor unit analysis showed a mean increase of 36% in motor unit amplitude (p = 0.045), 22% increase in duration (p = 0.005) and 29% increase in number of phases (p = 0.002). CONCLUSIONS: Mononuclear cell injection in partly denervated muscle of brachial plexus patients is safe. The results suggest enhanced muscle reinnervation and regeneration. Cite this article: Bone Joint Res 2014;3:38-47.

Carotid body tumors are not associated with an increased risk for sleep-disordered breathing.

PURPOSE: Tumors in the carotid bodies may interfere with their function as peripheral chemoreceptors. An altered control of ventilation may predispose to sleep-disordered breathing. This study aimed to assess whether patients with unilateral or bilateral carotid body tumors (uCBT or bCBT, respectively) or bilateral CBT resection (bCBR) display sleep-disordered breathing and to evaluate the global contribution of the peripheral chemoreceptor to the hypercapnic ventilatory response. METHODS: Eight uCBT, eight bCBT, and nine bCBR patients and matched controls underwent polysomnography. The peripheral chemoreflex drive was assessed using euoxic and hyperoxic CO2 rebreathing tests. Daytime sleepiness and fatigue were assessed with the Epworth Sleepiness Scale and the Multidimensional Fatigue Index. RESULTS: All patient groups reported significant fatigue-related complaints, but no differences in excessive daytime sleepiness (EDS) were found. The apnea/hypopnea index (AHI) did not differ significantly between patient groups and controls. Only in bCBT patients, a trend towards a higher AHI was observed, but this did not reach significance (p=0.06). No differences in the peripheral chemoreflex drive were found between patients and controls. CONCLUSIONS: Patients with (resection of) CBTs have more complaints of fatigue but are not at risk for EDS. The presence or resection of CBTs is neither associated with an altered peripheral chemoreflex drive nor with sleep-disordered breathing.

Patients previously treated for nonfunctioning pituitary macroadenomas have disturbed sleep characteristics, circadian movement rhythm, and subjective sleep quality.

CONTEXT AND OBJECTIVE: Fatigue and excessive sleepiness have been reported after treatment of nonfunctioning pituitary macroadenomas (NFMA). Because these complaints may be caused by disturbed nocturnal sleep, we evaluated objective sleep characteristics in patients treated for NFMA. DESIGN: We conducted a controlled cross-sectional study. SUBJECTS AND METHODS: We studied 17 patients (8 women; mean age, 54 yr) in remission of NFMA during long-term follow-up (8 yr; range, 1-18 yr) after surgery (n = 17) and additional radiotherapy (n = 5) without comorbidity except for hypopituitarism and 17 controls matched for age, gender, and body mass index. Sleep was assessed by nocturnal polysomnography, sleep and diurnal movement patterns by actigraphy, and quality of life and subjective sleep characteristics by questionnaires. RESULTS: Compared to controls, patients had reduced sleep efficiency, less rapid eye movement sleep, more N1 sleep, and more awakenings in the absence of excessive apnea or periodic limb movements. Actigraphy revealed a longer sleep duration and profound disturbances in diurnal movement patterns, with more awakenings at night and less activity during the day. Patients scored higher on fatigue and reported impaired quality of life. CONCLUSION: Patients previously treated for NFMA suffer from decreased subjective sleep quality, disturbed distribution of sleep stages, and disturbed circadian movement rhythm. These observations indicate that altered sleep characteristics may be a factor contributing to impaired quality of life and increased fatigue in patients treated for NFMA.

Efficacy of 3,4-diaminopyridine and pyridostigmine in the treatment of Lambert-Eaton myasthenic syndrome: a randomized, double-blind, placebo-controlled, crossover study.

3,4-Diaminopyridine and pyridostigmine are widely used to treat Lambert-Eaton myasthenic syndrome (LEMS), either alone or in combination. 3,4-Diaminopyridine enhances the release of acetylcholine at the neuromuscular synapse, and pyridostigmine inhibits the degradation of this neurotransmitter. Although this could lead to a synergistic effect on neuromuscular transmission, no studies have compared the effects of these drugs in patients with LEMS. Therefore, we performed a placebo-controlled, double-dummy, double-blind, randomized, crossover study in nine patients with LEMS.

Single-fiber EMG in familial hemiplegic migraine.

Twelve familial hemiplegic migraine (FHM) patients (6 with the I1811L mutation in CACNA1A, 3 with M731T mutation in ATP1A2, and 3 without known mutations) and 10 control subjects underwent single-fiber EMG. Mean jitter did not differ significantly between patients and control subjects or among patients. No blocking was found. The results suggest that neuromuscular function is normal in FHM.

Diagnostic value of history taking in reflex syncope.

The medical history, in combination with the physical examination and a 12-lead electrocardiogram, plays a key role in the diagnosis and risk stratification of patients with syncope. However, diagnostic clinical criteria are not uniformly applied. In older studies, the diagnostic criteria for vasovagal or reflex syncope often included typical precipitating events and warning symptoms. More recent studies have documented that a variety of unrecognized stressors can trigger reflex syncope and that warning signs and symptoms may be minimal. A characteristic medical history (a trigger and/or prodromi) is enough to diagnose reflex syncope if the risk for a cardiac cause of syncope is low (e. g. patients < 65 yrs, without a history of heart disease and no ECG abnormalities). In elderly subjects with a higher risk of cardiac syncope, the yield of the medical history is lower. However, a prospective study of the value of the medical history for the diagnosis of syncope with long-term follow-up has not been performed.

Long-term results of anterior anal sphincter repair for fecal incontinence due to obstetric injury / with invited commentaries.

AIMS: This study is to report short- and long-term results of anterior sphincter repair for fecal incontinence due to obstetric injury and factors predicting an unsuccessful outcome. METHODS: Thirty-nine consecutive patients, mean age 51 years (range 29-74), who underwent anterior sphincter repair for fecal incontinence due to obstetric injury were investigated. Duration of symptoms ranged from 9 months to 34 years. All patients underwent an anterior overlapping sphincter muscle reconstruction and in most cases a puborectal muscle plasty. RESULTS: Three months after surgery 77% of the patients had regained continence (Parks score of 1 or 2), at 9 months 67% were continent and after 12 months or more (mean, range 12-114) only 62%. Patients with prolonged pudendal latency (>2.2 ms) did significantly worse than patients without it (p < 0.05). Patients who had had lateral episiotomy during labor had significantly better outcome than those without it (p < 0.05). CONCLUSION: The outcome of anterior sphincter repair deteriorates with time after surgery. Assessment should be done at least 1 year after surgery to evaluate the final results of anterior sphincter repair. Prolonged pudendal latency predicts a poor outcome of anterior sphincter repair, and a prior lateral episiotomy is possibly a good prognostic factor.

Acquired slow-channel syndrome: a form of myasthenia gravis with prolonged open time of the acetylcholine receptor channel.

A 32-year-old female presented with a 2-year history of fluctuating generalized weakness including extraocular, bulbar, and limb muscles, suggesting myasthenia gravis, but with poor response to pyridostigmine and unusual electromyographic findings. After rest, power increased on repeated maximal contractions, followed by progressive weakness. There were decremental responses at low-frequency stimulation, but incremental responses at high frequencies, and single stimuli evoked repetitive compound muscle action potentials. Plasmapheresis was ineffective. In a conventional assay, antibodies against acetylcholine receptors (AChRs) were borderline. However, in an assay using cells expressing mainly adult-type human AChRs, the patient's serum was positive. Thymectomy revealed a hyperplastic thymus. An intercostal muscle specimen revealed small miniature end-plate potentials, 0.22+/-0.02 mV instead of 0.56+/-0.05 mV in controls. The number of 125I-alpha-bungarotoxin binding sites was normal. The decay time constant of end-plate potentials was increased from 5.3+/-0.6 msec in controls to 23+/-3.6 msec in the patient. Ultrastructurally, there was no destruction of the end plate. Transfer of the patient's plasma to mice in vivo produced similar physiological changes in their diaphragms. We conclude that the patient has an immune-mediated disorder, in which an antibody specific to the adult form of the AChRs alters the channel properties, reducing total current and slowing the closure. We propose the name "acquired slow-channel syndrome" for this variant of myasthenia gravis.

['Inclusion body'-myositis]. / 'Inclusion body'-myositis.

In 3 patients, a 72-year-old man, a 62-year-old man and a 73-year-old woman with weakness of respectively the quadriceps femoris, the finger flexors and the pharyngeal muscles, the diagnosis of 'inclusion body myositis' was made. This is a rare, slowly progressive skeletal muscle disorder which is more common in men and after the age of fifty. The activity of serum creatine kinase is often 2-5 times the highest normal value. The electromyogram pattern is myopathic, but can also display neuropathic changes (exclusively). Inclusion body myositis is often misdiagnosed, which can lead to an inappropriate treatment or approach. A frozen muscle biopsy is needed to make cryostat sections for demonstration of myositis with rimmed vacuoles.

Periodic fever associated with intermittent rhythmic delta activity: a syndrome of hypothalamic origin?

We report the case of a patient with a 16 year history of periodic (30 day cycle) fever attacks. The infradian cycle, associated clinical features, and the findings of electroencephalogram recorded during two fever attacks suggest a periodic hypothalamic syndrome.

Repetitive CMAPs: mechanisms of neural and synaptic genesis.

Repetitive compound muscle action potentials (R-CMAPs) occur when a single nerve shock excites muscle fibers repeatedly. "Double discharges" are due to intramuscular nerve reexcitation. "Synaptic" R-CMAPs, due to excess acetylcholine in the neuromuscular synapse, can occur in congenital myasthenia, the slow-channel syndrome, and acetylcholinesterase inhibition. Secondary nerve excitation can reexcite muscle fibers. Synaptic R-CMAPs in a patient consisted of two discharges. The second diminished during repetitive stimulation and began 3.5-4.0 ms after the first, which is slightly longer than the synapse-muscle refractory period. Neural R-CMAPs, due to ectopic nerve activity, occur in neuromyotonia (NMT). R-CMAPs in a patient consisted of about 20 discharges at 200-300 Hz. Studies in healthy subjects showed that such trains represent added single CMAPs. Impulse frequency in the patient lied close to the threshold of refractoriness. Refractoriness of the synapse-muscle cell assembly determines the characteristics of R-CMAPs regardless of the primary cause.

Reinnervation of avulsed and reimplanted ventral rootlets in the cervical spinal cord of the cat.

Spinal nerve root avulsions frequently occur in brachial plexus injuries caused by traction. Such lesions are considered to afflict the central nervous system (CNS) and are, therefore, believed to be beyond surgical repair. The present experimental study was initiated to challenge this hypothesis. The ventral rootlets of C-7 were avulsed from the spinal cord in 28 cats via an anterior approach and subsequently reimplanted into the cord at the site of origin. In nonoperated control cats and cats undergoing reimplantation, electrophysiological experiments were performed and horseradish peroxidase was administered to the spinal nerve on the reimplanted side after survival times ranging from 6 to 293 days. Spinal cord sections in all cats were stained for neurofilament, acetylcholinesterase (AChE), Nissl, and glial fibrillary acidic protein. Horseradish peroxidase-labeled ventral horn motoneurons were found as early as 14 days after reimplantation and their number increased with time. On Days 209 and 293, the number of labeled neurons equaled the number of labeled ventral horn neurons in the two control cats that did not undergo surgery. Starting on Day 6 after reimplantation, the appearance of the ventral horn and the white matter in the neurofilament, AChE, and Nissl-stained sections changed as a result of the CNS response to the injury. A return to their normal appearance could be observed in these stainings from Day 209 onward. Glial fibrillary acidic protein-positive astrocytic tissue was consistently found in the ventral horn and in the white matter reimplantation area. From Day 69 onward, electrophysiological stimulation of the spinal nerve C-7 on the reimplanted side elicited an electromyogram response in the spinodeltoid muscle. The latency and threshold intensity of the C-7 responses were initially increased but equalized to match the nonoperated controls between 98 and 122 days after reimplantation. The results of this study show that functional regeneration of ventral horn neurons after root avulsion and subsequent reimplantation in the cat is possible.

Residual cognitive dysfunctioning at 6 months following coronary artery bypass graft surgery.

Neuropsychological testing is a sensitive method for quantitative assessment of cognitive dysfunctioning following cardiopulmonary bypass (CPB). However, the methodological problems associated with this method, such as learning effects due to repeated testing and the effects of distress on test performance, have often been underestimated. In this study, these confounding effects were controlled for by including the spouses of patients, exposed to the same potential stress effects associated with the operation, as a nonsurgical control group. The experimental group consisted of 63 patients (40-75 years) undergoing elective coronary artery bypass graft (CABG) surgery. A battery of standardized neuropsychological tests was administered to both groups 2 weeks preoperatively and 1 week, 1 month, and 6 months postoperatively. Statistical testing of inter-group differences in preoperative to postoperative changes in test performance revealed the following results: (1) For immediate memory and learning, in general test scores showed the same time course for both groups. (2) For recent memory, patients' scores showed a significant deterioration at 1 month after CABG surgery compared with the scores of spouses. This effect had not completely disappeared at 6 months postoperatively. (3) For attention and psychomotor speed as well as verbal fluency, patients' scores had deteriorated significantly at 1 week after surgery, with incomplete recovery at 6 months. These negative cognitive effects were not related to the patients' ages or CPB parameters (duration of CPB, aortic cross-clamp time, mean flow and arterial pressure during CPB and aortic cross-clamping, and minimum nasopharyngeal temperature). No differences in self-ratings of mood over time were found between the patients and spouses. The results indicate that, when adequately controlling for the effects of learning and distress, some cognitive functions are still impaired at 6 months after CABG surgery.

Variability of the main sequence.

PURPOSE: This study investigated the relationship between amplitude and peak velocity of saccadic eye movements (the so-called main sequence) and the intra-individual variability of the main sequence. METHODS: Saccadic amplitudes and peak velocities were measured twice in 58 healthy subjects with an infrared reflection technique. RESULTS: Considerable intra-individual variability was found between the first and second recordings. CONCLUSIONS: Intra-individual variability of saccadic peak velocity affects the interpretation of changes in repeated recordings of peak velocities, such as before and after medication is administered. Furthermore, considerable intra-individual variability decreases the probability that statistically significant differences between patients and control subjects can be detected, especially when groups are small. Calculating the intraclass correlation coefficient allows the number of subjects in comparative studies to be determined.

Trigeminal neuralgia-like pain in an aged woman with fibrous dysplasia of the skull base.

A 72 year old woman with attacks of severe lancinating pain in the right frontotemporal region of her face had, on CT scan of the skull base, fibrous dysplasia of the right sphenoid bone, involving the areas traversed by the trigeminal nerve. Her pain ceased following treatment with methysergide. In patients with hemifacial pain but no evident facial or skull deformities, CT scan of the skull base may be helpful in elucidating the diagnosis.