Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration.

Hypoxia stimulates angiogenesis through the binding of hypoxia-inducible factors to the hypoxia-response element in the vascular endothelial growth factor (Vegf) promotor. Here, we report that deletion of the hypoxia-response element in the Vegf promotor reduced hypoxic Vegf expression in the spinal cord and caused adult-onset progressive motor neuron degeneration, reminiscent of amyotrophic lateral sclerosis. The neurodegeneration seemed to be due to reduced neural vascular perfusion. In addition, Vegf165 promoted survival of motor neurons during hypoxia through binding to Vegf receptor 2 and neuropilin 1. Acute ischemia is known to cause nonselective neuronal death. Our results indicate that chronic vascular insufficiency and, possibly, insufficient Vegf-dependent neuroprotection lead to the select degeneration of motor neurons.

Spinal fluid evacuation may provide temporary relief for patients with unexplained widespread pain and fibromyalgia.

Fibromyalgia (FM) exhibits characteristics of a neurological disorder, and similarities have been identified between FM and idiopathic intracranial hypertension (IICH). When intracranial pressure rises, the drainage of excess cerebrospinal fluid (CSF) through the subarachnoid space of the cranial and spinal nerves increases. Higher CSF pressure irritates nerve fibers inside nerve root sheaths and may consequently cause radicular pain, as was reported in patients with IICH. Moreover, the cut-off of 20-25 cm H20 used to define IICH may be too high, as has been suggested in patients with chronic fatigue syndrome. We hypothesize that the neurological symptoms of FM are caused by the dysregulation of cerebrospinal pressure (CSP) and that spinal fluid drainage can relieve this pain. Exploring the processes underlying increased CSP may provide an alternative explanation for the generation of unexplained widespread pain (WSP) and FM as opposed to central sensitization. Additionally, when performing a lumbar puncture for diagnostic reasons, it is useful to measure opening pressure in patients with chronic WSP.

Fibromyalgia and unexplained widespread pain: The idiopathic cerebrospinal pressure dysregulation hypothesis.

Fibromyalgia (FM) is a debilitating, widespread pain disorder that is assumed to originate from inappropriate pain processing in the central nervous system. Psychological and behavioral factors are both believed to underlie the pathogenesis and complicate the treatment. This hypothesis, however, has not yet been sufficiently supported by scientific evidence and accumulating evidence supports a peripheral neurological origin of the symptoms. We postulate that FM and several unexplained widespread pain syndromes are caused by chronic postural idiopathic cerebrospinal hypertension. Thus, the symptoms originate from the filling of nerve root sleeves under high pressure with subsequent polyradiculopathy from the compression of the nerve root fibers (axons) inside the sleeves. Associated symptoms, such as bladder and bowel dysfunction, result from compression of the sacral nerve root fibers, and facial pain and paresthesia result from compression of the cranial nerve root fibers. Idiopathic Intracranial Hypertension, Normal Pressure Hydrocephalus and the clinical entity of symptomatic Tarlov cysts share similar central and peripheral neurological symptoms and are likely other manifestations of the same condition. The hypothesis presented in this article links the characteristics of fibromyalgia and unexplained widespread pain to cerebrospinal pressure dysregulation with support from scientific evidence and provides a conclusive explanation for the multitude of symptoms associated with fibromyalgia.

American football and other sports injuries may cause migraine/persistent pain decades later and can be treated successfully with electrical twitch-obtaining intramuscular stimulation (ETOIMS).

INTRODUCTION: Autonomous twitch elicitation at myofascial trigger points from spondylotic radiculopathies-induced denervation supersensitivity can provide favourable pain relief using electrical twitch-obtaining intramuscular stimulation (ETOIMS). AIM: To provide objective evidence that ETOIMS is safe and efficacious in migraine and persistent pain management due to decades-old injuries to head and spine from paediatric American football. METHODS AND MATERIALS: An 83-year-old mildly hypertensive patient with 25-year history of refractory migraine and persistent pain self-selected to regularly receive fee-for-service ETOIMS 2/week over 20 months. He had 180 sessions of ETOIMS. Pain levels, blood pressure (BP) and heart rate/pulse were recorded before and immediately after each treatment alongside highest level of clinically elicitable twitch forces/session, session duration and intervals between treatments. Twitch force grades recorded were from 1 to 5, grade 5 twitch force being strongest. RESULTS: Initially, there was hypersensitivity to electrical stimulation with low stimulus parameters (500 µs pulse-width, 30 mA stimulus intensity, frequency 1.3 Hz). This resolved with gradual stimulus increments as tolerated during successive treatments. By treatment 27, autonomous twitches were noted. Spearman's correlation coefficients showed that pain levels are negatively related to twitch force, number of treatments, treatment session duration and directly related to BP and heart rate/pulse. Treatment numbers and session durations directly influence twitch force. At end of study, headaches and quality of life improved, hypertension resolved and antihypertensive medication had been discontinued. CONCLUSIONS: Using statistical process control methodology in an individual patient, we showed long-term safety and effectiveness of ETOIMS in simultaneous diagnosis, treatment, prognosis and prevention of migraine and persistent pain in real time obviating necessity for randomised controlled studies.

Chronic refractory myofascial pain and denervation supersensitivity as global public health disease.

Chronic pain with a 30.3% global prevalence significantly impacts universal health. Low back pain has a 9.4% prevalence worldwide causing the most widespread disability. Neck pain ranks 4th highest regarding years lived with disability with a 4.9% prevalence worldwide. The principal cause of pain in 85% of patients visiting a tertiary pain clinic has a myofascial origin. The root cause is multifocal neuromuscular ischaemia at myofascial trigger points from muscle tightening and shortening following spondylotic radiculopathy induced partial denervation. Chronic refractory myofascial pain (CRMP) is a neuromusculoskeletal disease needing management innovations. Using electrical twitch-obtaining intramuscular stimulation (eToims), we provide objective evidence of denervation supersensitivity in multiple myotomes as cause, aggravation and maintenance of CRMP. This study underscores our previous findings that eToims is safe and efficacious for long-term use in CRMP. eToims aids potential prevention (pre-rehabilitation), simultaneous diagnosis, treatment (rehabilitation) and prognosis in real time for acute and CRMP management.

Lumbrical sparing in carpal tunnel syndrome: anatomic, physiologic, and diagnostic implications.

Motor axons supplying lumbrical muscles are less severely affected than axons supplying thenar muscles in the carpal tunnel syndrome; sometimes lumbrical motor fibers are less affected than digit 2 sensory fibers. This pattern is consistent with compression of both the anterior and posterior aspects of the median nerve in the carpal tunnel because nerve fibers responsible for thenar, lumbrical, and digit 2 functions lie in an anterior-posterior gradient within the distal median nerve. Recognition of lumbrical sparing supports the electrodiagnosis of carpal tunnel syndrome when the distal latency to thenar muscles or the palm-to-wrist mixed median nerve conduction velocity is normal.

Phrenic nerve dysfunction after heart-lung and lung transplantation.

BACKGROUND: Phrenic nerve dysfunction (PND) is a well-known complication after cardiac surgery, but reports on its incidence and consequences after heart-lung and lung transplantation are scarce. METHODS: The incidence and consequences (ventilator days and intensive-care unit length of stay [ICU LOS]) of PND were studied by retrospective chart review of 27 heart-lung (HLTx) and 111 lung (LTx) transplantations performed from July 1991 to June 2001 at the Leuven University Hospital, Leuven, Belgium. On clinical suspicion of diaphragmatic dysfunction, nerve conduction studies were performed, which were completed with a needle electromyogram (EMG) of the diaphragm when the conduction study was non-conclusive. RESULTS: The incidence of PND in 21 evaluable HLTx recipients was 42.8% (9 of 21 patients), resulting in significantly more ventilator days for PND patients (37.6 +/- 36.3 days vs 5.3 +/- 3 days; p < 0.05) and a prolonged ICU LOS (46.8 +/- 33 vs 9.8 +/- 4.9 days; p < 0.05). In the 97 evaluable LTx patients, 9.3% (9 of 97 patients) developed PND. This resulted in more ventilator days for the PND group (30.6 +/- 14.8 days vs non-PND 7.9 +/- 14.8 days. p < 0.05) and a longer ICU LOS (PND 37.8 +/- 18.7 days vs non-PND 12.1 +/- 17.8 p < 0.05). Needle EMG of the diaphragm revealed denervation in 1 HLTx and 5 LTx patients. In LTx patients sustaining PND more tracheostomies were performed (44.4% vs 4.5% for non-PND patients p < 0.005). Eight of 9 LTx patients with PND had sequential single-lung transplantation. CONCLUSIONS: PND represents an important clinical problem after HLTx and LTx and has a considerable influence on both number of ventilator days and ICU resource utilization.

Brachial plexus neuritis following HPV vaccination.

We present a 19-year-old girl who developed a left brachial plexus neuritis following vaccination with a quadrivalent human papillomavirus (HPV) vaccine. Post-vaccination brachial plexus neuritis is a rare event. Nevertheless, this first case warrants careful attention in view of the large vaccination campaigns in young adolescents being launched all over the world.

Insulin therapy protects the central and peripheral nervous system of intensive care patients.

OBJECTIVE: To investigate the effectiveness of maintaining blood glucose levels below 6.1 mmol/L with insulin as prevention of secondary injury to the central and peripheral nervous systems of intensive care patients. METHODS: The authors studied the effect of intensive insulin therapy on critical illness polyneuropathy (CIPNP), assessed by weekly EMG screening, and its impact on mechanical ventilation dependency, as a prospectively planned subanalysis of a large randomized, controlled trial of 1,548 intensive care patients. In the 63 patients admitted with isolated brain injury, the authors studied the impact of insulin therapy on intracranial pressure, diabetes insipidus, seizures, and long-term rehabilitation at 6 and 12 months follow-up. RESULTS: Intensive insulin therapy reduced ventilation dependency (p = 0.0007; Mantel-Cox log rank test) and the risk of CIPNP (p < 0.0001). The risk of CIPNP among the 405 long-stay (> or =7 days in intensive care unit) patients was lowered by 49% (p < 0.0001). Of all metabolic and clinical effects of insulin therapy, and corrected for known risk factors, the level of glycemic control independently explained this benefit (OR for CIPNP 1.26 [1.09 to 1.46] per mmol blood glucose, p = 0.002). In turn, prevention of CIPNP explained the ability of intensive insulin therapy to reduce the risk of prolonged mechanical ventilation (OR 3.75 [1.49 to 9.39], p = 0.005). In isolated brain injury patients, intensive insulin therapy reduced mean (p = 0.003) and maximal (p < 0.0001) intracranial pressure while identical cerebral perfusion pressures were obtained with eightfold less vasopressors (p = 0.01). Seizures (p < 0.0001) and diabetes insipidus (p = 0.06) occurred less frequently. At 12 months follow-up, more brain-injured survivors in the intensive insulin group were able to care for most of their own needs (p = 0.05). CONCLUSIONS: Preventing even moderate hyperglycemia with insulin during intensive care protected the central and peripheral nervous systems, with clinical consequences such as shortening of intensive care dependency and possibly better long-term rehabilitation.

Condensing osteitis of the clavicle. Report of two cases and review of the literature.

Condensing osteitis of the clavicle, better defined as aseptic enlarging osteosclerosis of the clavicle, is a rare and benign idiopathic lesion. It is probably of degenerative or mechanical origin, and is most commonly seen in middle-aged women as a tender swelling over the medial one-third of the clavicle. Although the clinical features may be confusing and nonspecific, the typical radiographic and histopathological findings will mostly lead to a correct diagnosis of this disorder. The differential diagnosis is quite extensive. Most difficult to differentiate are: avascular necrosis of the medial clavicular epiphysis, sternoclavicular orsteoarthritis, low-grade chronic osteomyelitis, sternocostoclavicular hyperostosis and Tietze's syndrome. The authors recommend a thorough physical examination and technical tests, not only in subjects with pain of the clavicle but also in those with shoulder pain only, especially in women who are in their fourth decade. Treatment with analgesic and anti-inflammatory medications may be variably effective. In refractory cases excisions of the medial one-third of the clavicle may be indicated to offer better relief of symptoms as well as to exclude malignancy.

Progressive teflon denudation of the monopolar needle: effects on motor unit potential parameters.

This paper reports on the effects of an increase in size of the recording surface of monopolar needles on motor unit potentials (MUPs). The teflon coating of the TECA monopolar needles MG37 and MF37, commonly used in clinical electromyography, was progressively denuded to increase the length of the recording tip to 2, 3, 5, and 10 times the normal exposure, with resultant increase in the area of the recording portion. Low threshold MUPs obtained on minimal contraction from the tibialis anterior were analyzed for amplitude, duration, area, phases, turns, peak duration, and index. The amplitude and area of the MUP showed the most change, both decreasing with progressive denudation. The number of turns and phases were also reduced, more for the MF than for the MG needle. Duration, peak duration, and index showed insignificant changes. These findings give further support to the use of duration for representation of the MUP, since this is the most stable parameter even under poor recording conditions.

Electrical injuries to peripheral nerves.

As people come frequently into contact with electrical power sources, electrical injuries to peripheral nerves are commonly seen. The authors first review the parameters determining the severity and distribution of electrical injury to nerve tissue. These include tissue resistance, tissue susceptibility, current pathway, type of current, current density, duration and size of electrical contact. Subsequently, the pathophysiology of electrical injuries to nerve tissue is reviewed. Such injuries can be the result of thermal damage, vascular impairment, histological or electrophysiological changes in peripheral nerves, or direct mechanical trauma. Each of these types of injuries causes, specific lesions. As these lesions, especially delayed peripheral neurologic injury, can cause medico-legal problems, it is important to emphasize that electroneuromyography must be performed as early as possible.

Study of single motor unit discharge patterns using 1/f process model.

We developed a technique to study temporal discharge patterns of single motor units using 1/f process model, whose fractional parameter gamma was shown to be a useful indicator for distinguishing between discharge behaviors of single motor units of normal subjects and patients with upper motor neuron lesions. We have studied a total of 47 motor units in 3 normal subjects, and 41 in 3 patients with upper motor neuron lesions from biceps and extensor digitorum communis muscles during steady contraction. The parameter gamma was estimated with an algorithm based on wavelet analysis. The mean value of gamma in patients was 1.52, and the mean value of gamma in normal subjects was -0.06. These results suggest that 1/f process can be used to document the impaired motor control mechanisms at single motor unit level.

Electromyographic findings in ilioinguinal-iliohypogastric nerve entrapment syndrome.

The ilioinguinal-iliohypogastric nerve entrapment syndrome is a recognised cause of, usually chronic, lower abdominal pain. Diagnosis is based upon a typical clinical triad and relief of pain by injection of a local anaesthetic. In the present study we assessed the value of abdominal muscle electromyography in 41 patients with a clinical syndrome suggestive of ilioinguinal-iliohypogastric nerve entrapment. Electromyographic abnormalities were detected in 15 of 25 cases (60%) with definite diagnosis and in 6 of 16 (37%) of those with probable diagnosis of ilioinguinal-iliohypogastric nerve entrapment syndrome. The rather low sensitivity and the clinical value of this technique are discussed.

Value of somatosensory and motor evoked potentials in predicting arm recovery after a stroke.

OBJECTIVES: Prediction of motor recovery in the arm in patients with stroke is generally based on clinical examination. However, neurophysiological measures may also have a predictive value. The aims of this study were to assess the role of somatosensory (SSEPs) and motor (MEPs) evoked potentials in the prediction of arm motor recovery and to determine whether these measures added further predictive information to that gained from clinical examination. METHODS: Sixty four patients who had had a stroke and presented with obvious motor deficit of the arm were examined in terms of three clinical variables (motor performance, muscle tone, and overall disability) and for SSEPs and MEPs. Clinical and neurophysiological examinations were done at entry to the study (2 to 5 weeks poststroke), and at about 2 months after stroke. Further clinical follow up was conducted at 6 and 12 months after stroke. RESULTS: Neurophysiological measures made in the acute phase were of little use alone in predicting motor recovery of the arm at 2, 6, and 12 months after stroke. At 2 months, the absence of SSEPs and MEPs indicated a very poor outcome. Conversely, if the responses were preserved, a great variation in motor outcome was found. Multiple regression analysis showed that the addition of SSEPs and MEPs to the clinical examination increased the possibility of predicting arm recovery in the long term. In the acute phase, the combination of the motor score and SSEPs were best able to predict outcome. The long term outcome based on variables taken at 2 months, was best predicted through incorporating the three clinical measures and MEPs. CONCLUSIONS: Neurophysiological measures alone are of limited value in predicting long term outcome. However, predictive accuracy is substantially improved through the combined use of both of these measures and clinical variables.

Electromyography of the external anal sphincter muscle during urodynamic testing in children with meningomyelocele.

In this study the correlation between the electromyographic examination of the external sphincter muscle and the urodynamic findings in patients with meningomyelocele was evaluated. Urodynamic testing, consisting of cystometry with bladder, urethral and abdominal pressure monitoring was performed with simultaneous electromyography of the external and sphincter muscle in 61 children, 29 boys and 32 girls, divided in groups according to age and to the level of lesion. Normal urodynamic studies were always correlated with normal external sphincter electromyography. In all patients with a high lesion and in 79% of all others detrusor hyperactivity was correlated with pathological sphincter electromyography. The clinical neurological level of the lesion was not correlated with the function of the detrusor-sphincter mechanism. In 29% of the patients examined with needle electromyography detrusor-sphincter dyssynergia was found, which is less than in most other published studies. And although dyssynergia is a risk factor for renal deterioration, the authors conclude that its effect on the ureter is less important than in subjects with normal perineal musculature, since 80% of the examined patients with meningomyelocele showed pathological sphincter electromyography. These findings thus show a significant correlation between electromyography of the external sphincter muscle and the urodynamic findings in meningomyelocele patients, and clearly demonstrate the importance of urodynamic testing with simultaneous external sphincter electromyography, in order to improve both diagnostic accuracy and reliability of follow-up and treatment.

The anterior compartment syndrome in the lower leg. Review and role of the EMG examination.

The Anterior Compartment Syndrome is a relatively rare affection with a wide spectrum of etiologies. Like every compartment syndrome, it is a condition in which high pressure in a rigid osteofascial space reduces capillary blood perfusion so that tissue viability is threatened. When pressure remains sufficiently high for a number of hours, normal muscle and nerve functions become disturbed which may lead to myoneural necrosis. Therefore, an early decompression by means of fasciotomy is essential. Clinical examination is of critical importance in reaching a diagnosis: first of all a painful swelling occurs, followed by muscular paresis or paralysis, and finally loss of sensation and a "silent" electromyogram (EMG). In some cases pressure measurements are necessary, in which tissue pressures over 30 to 40 mm Hg are considered abnormal. The EMG-examination is useful in order to achieve a diagnosis and to assess the degree of injury. It may be an important guide for further rehabilitation.

Motor unit synchronization in physiologic, enhanced physiologic, and voluntary tremor in man.

Synchronization between pairs of single motor units simultaneously recorded from wrist extensor muscles was quantitated in 3 normal subjects during physiologic tremor (PT), beta-adrenergically enhanced physiologic tremor (EPT), and fast voluntary wrist flexion-extension movements mimicking tremor (VT). Cross-correlation histograms generated from the two spike trains of each motor unit pair demonstrated central or paracentral peaks in 13/19 recordings during PT, 22/36 during EPT, and 6/7 during VT. Relative peak area was used as a quantitative index of synchronization between the two motor units of each pair. It was lowest in PT, progressively increased in EPT as tremor amplitude increased, and highest in VT. In PT and lower amplitude EPT, the synchronization indexes were higher between motor units that discharged at the same or nearly the same frequency. In contrast, in higher amplitude EPT and VT, motor units with different firing frequencies were sometimes strongly synchronized as a consequence of double discharges in faster-firing motor units that had burst repetition rates in the range of slower-firing motor units discharging as singlets. Greater motor unit synchronization with increasing tremor amplitude in EPT may be secondary to a simultaneous increase in muscle spindle afferent activity from the tremulous muscle. Greatest synchronization in VT presumably reflects near maximal supraspinal and segmental common synaptic input onto motoneurons that generate VT. These results support a longstanding hypothesis that synchronization of motor units is the physiological basis for higher amplitude tremor.