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Pain, muscle spasms and twitching fingers following brachial plexus avulsion. Report of three cases relieved by dorsal root entry zone coagulation.

Three patients who, following partial brachial plexus avulsion, experienced pain, involuntary finger twitching and muscular spasms are reported. Two exhibited cutaneous trigger zones, stimulation of which exacerbated their pain; changes in emotional tone aggravated both the pain and the spasms. Pain would appear to be due not only to deafferentation and scarring of the dorsal horn, but also to an afferent pathological barrage from partially damaged dorsal roots. The pathological sensory barrage may activate metameric interneuronal circuits and produce involuntary movements. Exacerbation of both the pain and the spasms can be explained on the basis of intrinsic properties of these ectopic pacemakers.

Adult↗

Diagonistic dyspraxia: case report and movement-related potentials.

We report unusual motor behavior of the left hand dissociated from conscious volition in a 51-year-old right-handed man. This patient had sustained damage to the anterior two-thirds of the corpus callosum, the rostral and lower parts of the right medial frontal lobe, and a small portion of the left medial frontal lobe. He subsequently showed 4 types of abnormal motor behavior in the left hand that were triggered by voluntary activities of the right hand: symmetric or antagonistic left hand movements; irrelevant movements of the left hand to the right hand; and a tendency to close the fingers of the left hand into a fist. Recordings of movement-related potentials revealed a marked attenuation of the Bereitschaftspotential (BP) over the right hemisphere observed only when the patient initiated voluntary activity with the right hand. Since the BP is believed to represent a cerebral cortical activity preparatory for voluntary movement, we infer that the level of dysfunction in this patient is at the motor preparatory level caused by a disconnection of the right hemisphere from the left.

Cerebral Hemorrhage↗

Nucleocytoplasmic traffic disorder induced by cardioviruses.

Some picornaviruses, for example, poliovirus, increase bidirectional permeability of the nuclear envelope and suppress active nucleocytoplasmic transport. These activities require the viral protease 2A(pro). Here, we studied nucleocytoplasmic traffic in cells infected with encephalomyocarditis virus (EMCV; a cardiovirus), which lacks the poliovirus 2A(pro)-related protein. EMCV similarly enhanced bidirectional nucleocytoplasmic traffic. By using the fluorescent "Timer" protein, which contains a nuclear localization signal, we showed that the cytoplasmic accumulation of nuclear proteins in infected cells was largely due to the nuclear efflux of "old" proteins rather than impaired active nuclear import of newly synthesized molecules. The nuclear envelope of digitonin-treated EMCV-infected cells permitted rapid efflux of a nuclear marker protein. Inhibitors of poliovirus 2A(pro) did not prevent the EMCV-induced efflux. Extracts from EMCV-infected cells and products of in vitro translation of viral RNAs contained an activity increasing permeability of the nuclear envelope of uninfected cells. This activity depended on the expression of the viral leader protein. Mutations disrupting the zinc finger motif of this protein abolished its efflux-inducing ability. Inactivation of the L protein phosphorylation site (Thr47-->Ala) resulted in a delayed efflux, while a phosphorylation-mimicking (Thr47-->Asp) replacement did not significantly impair the efflux-inducing ability. Such activity of extracts from EMCV-infected cells was suppressed by the protein kinase inhibitor staurosporine. As evidenced by electron microscopy, cardiovirus infection resulted in alteration of the nuclear pores, but it did not trigger degradation of the nucleoporins known to be degraded in the poliovirus-infected cells. Thus, two groups of picornaviruses, enteroviruses and cardioviruses, similarly alter the nucleocytoplasmic traffic but achieve this by strikingly different mechanisms.

Active Transport, Cell Nucleus↗

DM2 intronic expansions: evidence for CCUG accumulation without flanking sequence or effects on ZNF9 mRNA processing or protein expression.

Myotonic dystrophy type 2 (DM2) is caused by a CCTG expansion mutation in intron 1 of the zinc finger protein 9 (ZNF9) gene. The mean expansion size in patients is larger than for DM1 or any previously reported disorder (mean=5000 CCTGs; range=75-11 000), and similar to DM1, repeats containing ribonuclear inclusions accumulate in affected DM2 tissue. Although an RNA gain-of-function mechanism involving DM1 CUG or DM2 CCUG expansion transcripts is now well established, still debated are the potential role that flanking sequences within the DMPK 3'-UTR may have on disease pathogenesis and whether or not decreased expression of DMPK, ZNF9 or neighboring genes at these loci contribute to disease. To address these questions in DM2, we have examined the nucleic acid content of the ribonuclear inclusions and the effects of these large expansions on ZNF9 expression. Using cell lines either haploid or homozygous for the expansion, as well as skeletal muscle biopsy tissue, we demonstrate that pre-mRNAs containing large CCUG expansions are normally spliced and exported from the nucleus, that the expansions do not decrease ZNF9 expression at the mRNA or protein level, and that the ribonuclear inclusions are enriched for the CCUG expansion, but not intronic flanking sequences. These data suggest that the downstream molecular effects of the DM2 mutation are triggered by the accumulation of CCUG repeat tract alone.

3' Untranslated Regions↗

[The bereitschaftspotential. The concept and methodology for acquiring it].

INTRODUCTION: The movement of extension of the index finger in a stereotyped manner, not as a reaction to any external or internal stimulus, is preceded by EEG activity representing activity of the supplementary motor area of the motor cortex. DEVELOPMENT: By averaging retrograde EEG activity prior to movement, the Bereitschaftspotential (BP) may be obtained, using the German nomenclature of the earliest investigators who first described it and its components NS1 and NS2. We include a table with normal values obtained from a group of healthy persons. CONCLUSION: In our study we show the usefulness of off-line methodology with manual adjustment of the start of EMG activity to obtain better morphological definition and greater voltage of the BP. At the same time, continual acquisition with the trigger adjusted to a prefixed threshold (on-line methodology) means that a smaller BP is obtained, especially in persons with difficulty in the organization of this movement.

Adult↗

[Carpal tunnel syndrome and amyloid tenosynovitis in patients undergoing chronic hemodialysis. Evaluation and treatment apropos of 130 cases].

Over a 12-year period (1979-1991), 130 carpal tunnel syndromes were diagnosed in 89 haemodialysed renal failure patients, representing 17% of all haemodialysed patients followed over the same period. 6% of patients had been haemodialysed for less than 5 years (mean duration of dialysis: 10.4 years). 25% of cases had a trigger finger and 21 out of 89 patients had amyloid arthropathy. No precise relationship was detected between the side of the carpal tunnel syndrome and the side of the arteriovenous fistula. In 130 cases, release of the median nerve and wide tenosynovectomy of the flexor tendons were performed under pneumatic tourniquet except in the case of a prosthetic shunt. Tenosynovial amyloid deposits were found in 84% of cases. The mean postoperative follow-up was 40 months (range: 6 to 120 months). Postoperatively, the acroparaesthesiae disappeared in 93% of cases. 79% of cases with a sensory defect obtained sensory recovery, versus 27% of cases with a motor deficit for motor recovery. In 20% of the 130 cases, decreased digital mobility was observed postoperatively due to extension of the tenosynovitis to the fingers. Four cases of recurrence were observed.

Adult↗

Hypovolemic ischemic optic neuropathy.

BACKGROUND: Ischemic optic neuropathy refers to an acute event of ischemia, or decreased blood flow, to the optic nerve resulting in varying degrees of vision loss and visual field defects. Typically this disease affects the elderly population who experience systemic diseases that compromise the blood flow efficiency of the optic nerve head (e.g., giant-cell arteritis, hypertension, diabetes, etc.). However, cases of blood loss to the optic nerve, secondary to traumatic injuries or surgeries, have also been shown to result in ischemic optic neuropathy, regardless of age. It seems that in these cases, the resulting anemia and hypotension play contributing roles in the development of ischemic optic neuropathy. METHODS: A 41-year-old black man came to us with optic nerve head pallor O.S., count-fingers vision O.S., positive afferent pupillary defect O.S., and a central scotoma O.S. after being hospitalized and treated for a stab wound to his left neck that severed his left carotid artery at the bifurcation. RESULTS: This patient had been seen in the Optometry Clinic two years before the stab-wound incident. At that time, he had 20/20 vision in his left eye and no remarkable neurological deficits. His ocular presentation after the traumatic hypovolemic event was probably a direct result of the hypoperfusion to the left optic nerve head. This patient was diagnosed with a hypovolemic, or blood loss-related, ischemic optic neuropathy (O.S.). CONCLUSIONS: Patients who experience large amounts of blood loss due to trauma, surgery, internal bleeding, etc. and report vision loss should be screened for possible optic nerve ischemia. As eye care providers, when we are presented with patients who have optic nerve head atrophy, we should inquire about events that may have precipitated blood loss, potentially triggering ischemic optic neuropathy.

Adult↗

Management of severe toxic epidermal necrolysis in children.

Toxic epidermal necrolysis (TEN) is a severe form of erythema multiforme that results in extensive epidermal sloughing; the condition is associated with a mortality of up to 70%. From 1991 to 1998, 10 children with severe toxic epidermal necrolysis were referred to a regional pediatric burn facility. Wounds were managed with strategy involving prevention of wound desiccation and superinfection, including the frequent use of biologic wound coverings. Children unable to guard their airway because of extensive oropharyngeal involvement were prophylactically intubated. Enteral nutrition was stressed. Steroids were not used and antibiotics were administered to managed specific foci of infection only. The 2 boys and 8 girls had an average age of 7.2+/-1.8 years (range 6 months to 15 years) and sloughed surface area of 76+/-6% of the body surface (range 50 to 95%). Antibiotics (3 children), anticonvulsants (3 children), nonsteroidals (2 children), and viral syndrome or unknown agents (2 children) were felt to have triggered the syndrome. Six children (60%) required intubation for an average of 9.7+/-1.8 days (range 2 to 14 days). Buccal mucosal involvement occurred in 9 (90%) and ocular involvement in 9 (90%). Although infectious complications were common (2 pneumonias, 2 urinary infections, 1 bacteremia, 2 central line infections, and 2 candidemias), all children survived after lengths of stay in the burn unit averaging 19+/-3 (range 6 to 40) days. The most common long-term morbidity was keratitis sicca (2 children, 20%), finger nail deformities (3 children, 30%), and variegated skin pigment changes (5 children, 50%). Although having both a cutaneous and visceral wound that predispose them to infectious complications, most children with TEN will survive if managed with a strategy emphasizing biologic wound closure, intensive nutritional support, and early detection and treatment of septic foci. Burn units have the resource set required to manage severe TEN and early referral of such children may have a favorable impact on survival.

Adolescent↗

[My fingers itch, but my hands are bound. An exploratory psychosomatic study of patients with dyshidrosis of the hands (cheiropompholyx)].

The purpose of a pilot study with 20 patients, suffering from dyshidrotic exzema of the hands, was to investigate the relevance of a psychosomatic approach for its etiology and therapy. A set of psychological and allergological tests revealed the following results. - 10 patients suffered from a contact allergy (epicutaneous test), 6 of them were allergic to nickel - the patients were less aggressive and more permissive (Freiburger Personality Inventory; FPI) as compared to a standard population. They reported more somatic complaints (HHM) as healthy subjects. - the results of a semistructured interview support the hypothesis, that the dyshidrotic exzema often has an expressive function: the patients present their dependency conflict in a symbolic manner by means of their hands. They try to take their life in their own hands; autonomous actions however are hampered by their own dependency needs. The development of the dyshidrotic symptoms corresponds to the autonomy, which has been achieved with regard to the individual conflict of ambivalence. According to our findings the contact with nickel is not predominant, neither causative nor triggering, factor. Following the psychosomatic concept of Engel and Schmale, the authors discuss the pathogenesis of dyshidrosis with the meaning of a complication of (pregenital) conversion, with the hands as the part affected.

Adolescent↗

Intentional motor phantom limb syndrome.

OBJECTIVE: To investigate the clinical and anatomic correlates of a previously unreported form of chronic supernumerary phantom limb, which developed only in association with motor intent directed at a hemiplegic-anesthetic upper limb. METHODS: We explored the phenomenology of the phantom illusion in the light of motor control models. Hemodynamic correlates of supernumerary phantom limb were studied with an fMRI sensorimotor paradigm consisting of finger-thumb opposition movements. RESULTS: The kinesthetic-proprioceptive illusion of a third arm was triggered by any attempt to move the paretic limb, by bimanual actions, and by motor imagery involving the nonfunctional limb. The responsible lesion destroyed the posterior part of the posterior limb of the internal capsule on the opposite side, damaging corticospinal and thalamocortical tracts. Comparison between fMRI signals performed during virtual movement of the phantom hand vs imaginary movement of the paretic hand showed increased activation in thalamus and caudate nucleus in the first condition. CONCLUSIONS: A preserved sense of agency provided by intact premotor processes translating intention into action may lead to the vivid feeling of movement in a paralyzed limb, similar to kinesthetic illusions in amputees. The interruption of thalamic afferences may explain the persistence and stability of the phantom by preventing any correction of the mismatch between expected and effective movement. The increased blood oxygen level-dependent (BOLD) signal in the basal ganglia-thalamus-cortex pathway during movement of the supernumerary hand may reflect an abnormal closed-loop functioning of the thalamocortical system underlying the phantom phenomenon.

Aged↗

Behavioral treatment of migraine in children and adolescents.

Behavioral interventions, particularly biofeedback and relaxation therapy, have demonstrated their effectiveness in the treatment of both adults and older children with migraine in controlled trials. The physiological basis for their effectiveness is unclear, but data from one trial suggest that levels of plasma beta-endorphin can be altered by relaxation and biofeedback therapies. The data supporting the effectiveness of behavioral therapies are less clear-cut in children than in adults, but that is also true for the data supporting medical treatment. This is due in part to methodological issues, especially the lack of a specific test for migraine, which has hampered research and helped lead to an inappropriate de-emphasis on care for childhood headache. In addition, migraine headaches in children are often briefer and have a higher rate of spontaneous remission than those experienced by adults, making it difficult to separate effective from ineffective treatments. While it is widely believed that stress is a major factor in childhood migraine, well-designed studies have had difficulty developing data to support this viewpoint. Many clinicians utilize 'confident reassurance', reassuring the family that the child is not seriously ill, in the belief that having migraine headaches can be stressful. They also modify behaviors that are believed to trigger migraine headaches, such as poor sleep habits or irregular meal times. Relaxation therapies use techniques such as progressive relaxation, self-hypnosis, and guided imagery. Several studies have found relaxation therapies to be as effective, or more effective, in reducing the frequency of migraine headaches than modest doses of a beta-blockade medication, although one study found relaxation therapy to be no more effective than a control program. Several studies have demonstrated that these therapies can be taught to children in a low cost but effective manner. Biofeedback therapies commonly use an apparatus to demonstrate a physiological effect. Most commonly in pediatrics, children are taught to raise the temperature of one of their fingers. This can be done with or without a thermometer. Several groups have shown that these techniques can be taught to children and that their use is associated with fewer and briefer migraine headaches. People who experience migraines can also experience episodic headaches throughout life. An important consideration is preparing children to deal with future headaches, allowing them to feel in control of their health. Behavioral therapies have the potential to do this, giving the child access to a technique that can be easily resumed without a medical visit or prescription.

Adolescent↗

Consequences of recurrent phosphate trapping induced by repeated injections of 2-deoxy-D-galactose. Biochemical and morphological studies in rats.

2-Deoxy-D-galactose, in a dose of 3 mmol/kg, was administered intraperitoneally twice daily to young rats for periods up to 12 weeks. This dosage schedule resulted in recurrent phosphate trapping predominantly in liver. UTP deficiency was excluded by simultaneous uridine injections. Phosphate trapping was caused by the rapid accumulation of 2-deoxy-D-galactose 1-phosphate and was most pronounced in liver but also demonstrated in small intestine, brain, spleen, and thymus. The marked, although transient, drop in the hepatic content of inorganic phosphate triggered the catabolism of adenine nucleotides and a loss of ATP. Other metabolic pathways affected by phosphate deficiency include glycogenolysis and glycolysis. Increasing with time, repeated doses of the galactose analog led to retardation and arrest of growth, hepatomegaly, and splenomegaly. The average relative liver and spleen weights were elevated 2.5- and 4.5-fold, respectively, after 12 weeks of treatment. Liver damage was indicated by hyperbilirubinaemia and a progressive rise in the activity in plasma of sorbitol dehydrogenase, alkaline phosphatase, and gamma-glutamyltransferase. Examination by light and electron microscopy showed increasing numbers of vacuoles, surrounded by a single membrane, in hepatocytes, sinusoidal endothelial cells, and Kupffer cells. Focal cytoplasmic degeneration in hepatocytes was occasionally indicated by formation of autophagic vacuoles and finger print lysosomes. Hepatocytes of 2-deoxy-D-galactose-treated rats showed a dissociation and fragmentation of the rough endoplasmic reticulum. Sinusoidal endothelial cells and Kupffer cells were markedly enlarged, the latter contained a PAS-positive but amylase resistant substance. Extrahepatic changes included an increased occurrence of vacuolated cells in thymus. Phosphate trapping and its metabolic consequences are common phenomena in the experimental injury induced b 2-deoxy-D-galactose and in some hereditary diseases such as uridylyltransferase deficiency galactosaemia, fructose intolerance and glucose-6-phosphatase deficiency.

Animals↗

[FGFR1 and MOZ, two key genes involved in malignant hemopathies linked to rearrangements within the chromosomal region 8p11-12].

Two distinct clinical syndromes have been associated with the p11.12 region of the short arm of chromosome 8: stem-cell myeloproliferative disorder (B-or T-cell lymphoblastic leukemia/lymphoma with myeloid hyperplasia and peripheral blood eosinophilia) and acute myeloid leukemia (myelomonocytic or monocytic with erythrophagocytosis). The FGFR1 and MOZ genes are rearranged in these diseases and encode one of the four fibroblast growth factor receptors and a member of a novel histone acetyltransferase family, respectively. The predicted fusion proteins that are putatively oncogenic - FOP-FGFR1, CEP110-FGFR1, and FIM-FGFR1 - and - MOZ-CBP, MOZ-p300, and MOZ-TIF2 - lead to tumorigenesis through distinct pathways. The constitutive kinase activity triggered by dimerization mediated by the protein-protein interaction motifs of the FGFR1 protein partner regardless of external stimuli and the delocalization of the fusion proteins compared to their normal counterparts may lead to tumorigenesis presumably by inducing inappropriate recruitment in the cytoplasm of signaling substrates. Currently, little is known about the precise role of MOZ in the regulation of gene transcription. However, all the aberrant proteins described to date retain the MOZ histone acetyltransferase domain fused to that of the transcription coactivators CBP, p300, and TIF2. The fusion of two acetyltransferases whose activity may be mistargetted or misregulated could be a critical event in leukemogenesis. The increasing number of translocations affecting FGFR1 and MOZ strongly suggest their involvement in oncogenic processes and point to these proteins as potential therapeutical targets.

Acetyltransferases↗

Surgical treatment of carpal tunnel syndrome and trigger digits in children with mucopolysaccharide storage disorders.

The role of surgical intervention for carpal tunnel syndrome (CTS) and trigger digits in children with mucopolysaccharide storage disorders (MPSDs) has not been clearly defined, particularly as the treatment of the underlying disease has advanced to include bone marrow transplantation. This study reviews our experience in the treatment of CTS and trigger digits in 22 children with MPSDs who were evaluated for CTS by electromyographic (EMG)/nerve conduction velocity (NCV) testing. Seventeen children were diagnosed with CTS by EMG/NCV testing and were treated with bilateral open surgical release with or without flexor tenosynovectomy. The EMG/NCV testing revealed normal results in 5 patients who are subsequently being monitored. Forty-five digits in 8 children were diagnosed clinically with trigger digits. Nineteen digits were treated by annular pulley release alone. Twenty-six digits were treated by annular pulley release with partial flexor digitorum superficialis tendon resection. The average age at the time of hand surgery was 6.3 years, and at the time of follow-up, 9.6 years. Postoperative EMG/NCV testing in 7 children showed 1 with improvement and 6 with normalization. None of the patients undergoing carpal tunnel release went on to develop thenar atrophy or absent sensibility, as has been reported in untreated cases. Patients were evaluated for triggering digits both by preoperative tendon palpation and by intraoperative flexor tendon excursion at the time of open carpal tunnel release. All patients undergoing trigger release had improved active digital flexion seen at the final follow-up visit. Because of the very high incidence of CTS and trigger digits in this population, the authors currently recommend routine screening of EMG/NCV for all children with MPSDs. Early surgical intervention for nerve compression and stenosing flexor tenosynovitis can maximize hand function in these children.

Age Factors↗

Pharmacotherapy of Raynaud's phenomenon.

Primary Raynaud's phenomenon is common, particularly in younger women, and may be familial. Vasospasm is not confined to the digits and may involve, for example, the tongue and nose, and also visceral organs like the heart, oesophagus or lung and cerebral circulation. Symptoms tend to be milder in primary compared with secondary Raynaud's phenomenon, which is associated with other disorders such as the connective tissue diseases. Indeed, the severity of symptoms often acts as the predictor for the much later onset of the associated systemic disease. Occupational Raynaud's phenomenon is related to the use of vibrating instruments, and a significant proportion of patients may be cured by an early change in job. In those over 60 years of age, Raynaud's phenomenon is commonly a result of atherosclerotic obstructive arterial disease, and screening for and treatment of the risk factors is appropriate. The best-studied mechanisms in Raynaud's phenomenon involve the blood and vascular endothelium. Microcirculatory flow may be impeded by activated platelet clumps, rigid red and white blood cells and damaged endothelium. These platelet clumps, white blood cells and damaged endothelium also release vasoactive/vasoconstrictive compounds which may additionally trigger the clotting cascade and thrombosis. Initial management for mild disease should focus on support and advice regarding avoidance of known precipitating factors, including vasospastic drugs. Cold protection with warming agents, 'Abel' shoes and also electrically heated gloves and socks is effective, but may be too cumbersome and inconvenient for some patients. Simple vasodilators like naftidrofuryl, inositol nicotinate and possibly pentoxifylline (oxpentifylline) are useful in mild disease, with adverse effects like headache and flushing being less problematic. The 'gold standard' of Raynaud's phenomenon treatment is nifedipine, a calcium channel antagonist/blocker. Full dosage, however, can be limited by ankle swelling, headache and flushing, but adverse effects may be reduced by using the 'retard' or long-acting preparations. Adverse effects are also reduced with the newer calcium channel antagonists like diltiazem but at the expense of efficacy. Useful, enhanced benefit is also achieved by combination therapy with vasodilators. Newer treatments include the prostaglandin analogues which are effective but disadvantaged by their parenteral route of administration, and lack of licence in some countries. Oral preparations are, however, being studied and are in the pipeline. Essential fatty acid supplementation is mildly effective, while ketanserin and calcitonin gene-related peptide both look promising. Lumbar sympathectomy retains its important role in the treatment of Raynaud's phenomenon involving the lower limbs. Satisfactory symptomatic relief is now possible for many patients with Raynaud's phenomenon and this should certainly be the aim for all patients seeking medical help.

Calcium Channel Blockers↗