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Symptoms experienced by patients with carpal tunnel syndrome.

BACKGROUND: Patients with carpal tunnel syndrome (CTS) sometimes report sensory symptoms outside the median nerve distribution. This study was designed to provide a more detailed assessment of these symptoms. METHODS: Patients with clinical suspicion of upper limb neuromuscular lesions were divided into those with electrodiagnostic (EDX) evidence of CTS, and those without. CTS patients with superimposed nerve abnormalities were excluded. Motor and sensory symptoms were assessed in the exclusive CTS patients. RESULTS: Over 50% of patients with exclusive CTS reported tingling or numbness over the whole hand, ulnar or radial nerve distributions. Some patients reported symptoms proximal to the wrist. Sensory signs did not extend beyond the median nerve distribution. Numbness and nocturnal pain were predictive of positive EDX evidence of CTS. CONCLUSIONS: Sensory symptoms outside the distribution of the median nerve are common in CTS. For enhanced sensitivity in diagnosis it is useful to be aware of these "atypical" symptoms. Reports of numbness and nocturnal pain are strong indicators of CTS.

Adult↗

Identification of a human LNX protein containing multiple PDZ domains.

Recently PDZ domains have been recognized as crucial organizers of protein complexes at the plasma membrane. Here we report the cloning of a novel 3.7-kb cDNA LNX from a human fetal brain cDNA library. The deduced amino acid sequence shares about 88% identity with the p70 form of Lnx, which is the mouse ligand of Numb protein X. Motif analysis reveals five protein-interaction modules conservative to those in the Lnx protein, including four PDZ domains and a NPXY motif for binding of the Numb PTB domain. Northern blot analysis shows that the length of the transcript in brain is distinct from those in other tissues. By radiation hybrid mapping, we localize the LNX gene to human chromosome 4q12 between marker D4S1577 and marker D4S1594. We predict that LNX may be important for the organization of signaling complexes in Numb-involved pathways or pathways regulated by other PTB-containing proteins.

Amino Acid Motifs↗

Frizzled signalling controls orientation of asymmetric sense organ precursor cell divisions in Drosophila.

During metazoan development, cell-fate diversity is brought about, in part, by asymmetric cell divisions. In Drosophila, bristle mechanosensory organs are composed of four different cells that originate from a single precursor cell, pI, after two rounds of asymmetric division. At each division, distinct fates are conferred on sister cells by the asymmetric segregation of Numb, a negative regulator of Notch signalling. Here we show that the orientation of the mitotic spindles and the localization of the Numb crescent follow a stereotyped pattern. Mitosis of pI is orientated parallel to the anteroposterior axis of the fly. We show that signalling mediated by the Frizzled receptor polarizes pI along this axis, thereby specifying the orientation of the mitotic spindle and positioning the Numb crescent. The mitoses of the two cells produced by mitosis of pI are orientated parallel and orthogonal, respectively, to the division axis of pI. This difference in cell-division orientation is largely independent of the identity of the secondary precursor cells, and is regulated by Frizzled-independent mechanisms.

Animals↗

Bazooka recruits Inscuteable to orient asymmetric cell divisions in Drosophila neuroblasts.

Asymmetric cell divisions can be generated by the segregation of determinants into one of the two daughter cells. In Drosophila, neuroblasts divide asymmetrically along the apical-basal axis shortly after their delamination from the neuroectodermal epithelium. Several proteins, including Numb and Miranda, segregate into the basal daughter cell and are needed for the determination of its correct cell fate. Both the apical-basal orientation of the mitotic spindle and the localization of Numb and Miranda to the basal cell cortex are directed by Inscuteable, a protein that localizes to the apical cell cortex before and during neuroblast mitosis. Here we show that the apical localizaton of Inscuteable requires Bazooka, a protein containing a PDZ domain that is essential for apical-basal polarity in epithelial cells. Bazooka localizes with Inscuteable in neuroblasts and binds to the Inscuteable localization domain in vitro and in vivo. In embryos lacking both maternal and zygotic bazooka function, Inscuteable no longer localizes asymmetrically in neuroblasts and is instead uniformly distributed in the cytoplasm. Mitotic spindles in neuroblasts are misoriented in these embryos, and the proteins Numb and Miranda fail to localize asymmetrically in metaphase. Our results suggest that direct binding to Bazooka mediates the asymmetric localization of Inscuteable and connects the asymmetric division of neuroblasts to the axis of epithelial apical-basal polarity.

Animals↗

Asymmetric division and cosegregation of template DNA strands in adult muscle satellite cells.

Satellite cells assure postnatal skeletal muscle growth and repair. Despite extensive studies, their stem cell character remains largely undefined. Using pulse-chase labelling with BrdU to mark the putative stem cell niche, we identify a subpopulation of label-retaining satellite cells during growth and after injury. Strikingly, some of these cells display selective template-DNA strand segregation during mitosis in the muscle fibre in vivo, as well as in culture independent of their niche, indicating that genomic DNA strands are nonequivalent. Furthermore, we demonstrate that the asymmetric cell-fate determinant Numb segregates selectively to one daughter cell during mitosis and before differentiation, suggesting that Numb is associated with self-renewal. Finally, we show that template DNA cosegregates with Numb in label-retaining cells that express the self-renewal marker Pax7. The cosegregation of 'immortal' template DNA strands and their link with the asymmetry apparatus has important implications for stem cell biology and cancer.

Animals↗

Distinct expression patterns of splicing isoforms of mNumb in the endocrine lineage of developing pancreas.

The pancreas is composed of three tissues: endocrine, exocrine, and duct. The endocrine/exocrine lineages diverge from the ductal lineage before E12.5 in mice, and then further separate into endocrine and exocrine precursors. These processes are regulated by differential activation of Notch1-mediated signaling, which is required to repress the expression of the pro-endocrine gene neurogenin3 (ngn3) in the exocrine lineage. Mammalian Numb (mNumb) is an ortholog of Drosophila Numb (dNumb), which is likely to be an intracellular inhibitor of Notch signaling, and has four splicing isoforms: PTBS-PRRS, PTBL-PRRS, PTBS-PRRL, and PTBL-PRRL. Here we developed an anti-PRRL antibody, which recognizes only the PRRL forms of mNumb. We then performed immunohistochemical analyses using anti-PRRL together with anti-pan Numb, which recognizes all the isoforms of mNumb, antibodies that determine the spatio-temporal expression pattern of mNumb in the mouse fetal pancreas. mNumb PRRS and PRRL were first expressed in identical cells in the early stage of pancreatic development (i.e., E10.5), but gradually became biased. At the stage of endocrine and exocrine divergence, mNumb PRRS continued to be expressed in endocrine lineage cells, whereas PRRL was down-regulated during endocrine differentiation. Even after the endocrine/exocrine divergence, notch1 expression was sustained in endocrine lineage, where ngn3 was expressed. These results agree with the notion that mNumb PRRS has an inhibitory effect on Notch signaling, indicating its potential roles in the differentiation of pancreatic endocrine lineage. In addition, islet cells, which are produced from ductal tissue, were immunostained by the anti-panNb antibody. Our present results will contribute to the understanding of the mechanisms of islet development from ductal tissue.

Alternative Splicing↗

Paraneoplastic vasculitis associated with esophageal carcinoma.

We report a case of esophageal carcinoma associated with paraneoplastic vasculitis. A 69-year-old man suffered from low-grade fever and numbness of the lower limbs for 3 months before esophageal and gastric carcinomas were detected. Concurrent infection or collagen disease was ruled out following clinical and laboratory examinations. In April 1996, the gastric carcinoma was completely removed by endoscopic mucosal resection, but the symptoms remained. Three weeks later esophagectomy was performed for esophageal carcinoma after which time the fever and numbness disappeared. The esophageal carcinoma was a well-differentiated squamous cell carcinoma invading into the submucosal layer. Twenty-two lymph node metastases were found in 68 resected lymph nodes. Latent thyroid cancer was found. Histologically, vasculitis was detected in the esophagus, stomach and serratus anterior muscle. The distribution and degree of vasculitis were most pronounced in the esophagus. The concurrent onset and spontaneous resolution of fever and numbness after the removal of the esophageal carcinoma suggested a paraneoplastic origin. The majority of patients with malignant neoplasm-associated vasculitis had hematologic neoplasms. Cases of esophageal carcinoma associated with paraneoplastic vasculitis are extremely rare.

Aged↗

Shunting for syringomyelia in patients with spinal cord injuries: self-reported, long-term effects in 8 patients.

OBJECTIVE: To investigate the long-term effects of shunting on neurologic outcome of syringomyelia, a complication of spinal cord injury (SCI). DESIGN: Retrospective data collection using telephonic survey. SETTING: University based medical center. PARTICIPANTS: Eight of 15 patients who had shunts placed between 1976 and 1999. INTERVENTIONS: Review of clinical records and self-reported telephone interview. MAIN OUTCOMES MEASURES: Initial clinical presentation, recovery after shunt placement, and subsequent neurologic status were recorded. Patients were asked to rate symptomatic improvement after surgery on a 100-point analog scale; they were also asked whether they would have the surgery again. RESULTS: Presenting symptoms were weakness in all 8 patients, pain in 5 patients, and numbness in 5 patients. After shunting, 6 patients had improved strength, all had less pain, and 2 had less numbness. Six patients experienced neurologic decline an average of 2 years after shunt placement, 3 because of shunt failure, 2 from a new syrinx, and 1 from both shunt failure and new syrinx. Two of the 3 patients who underwent second shunt placements for a new syrinx had full neurologic recovery. Six patients said they would repeat the shunting procedure if necessary, 1 was uncertain, and 1 would not. CONCLUSION: Initial improvements noted after shunting provide long-lasting effects, even though many patients may need a second procedure. Less pain and improved strength are more significant than decreased numbness.

Cerebrospinal Fluid Shunts↗

Ropivacaine for dental anesthesia: a dose-finding study.

PURPOSE: The purpose of this study was to determine the optimal concentration and volumes of ropivacaine for dental anesthesia as regards onset and duration of action. SUBJECTS AND METHODS: Thirty healthy individuals with a mean age of 32 years participated in the study on a voluntary basis. All subjects received a ropivacaine injection in 1 of 3 randomized concentrations (2.0, 5.0, or 7.5 mg/mL) for infiltration anesthesia and mandibular nerve block in a double-blind manner. The onset time and duration of anesthesia were assessed by electric pulp test, pinprick test of the gingiva, and presence of feeling of numbness of the lip. RESULTS: Regardless of dose, only 5 patients received pulpal anesthesia after infiltration, but all 3 concentrations anesthetized the gingiva and upper lip. The onset of pulpal anesthesia occurred less than 5 minutes after injection and lasted for 4 to 58 minutes. Pinprick anesthesia lasted for 8 to 48 minutes, and numbness of the upper lip lasted 1 to 4 hours. The effectiveness of the mandibular nerve block with regard to pulpal anesthesia was dose dependent. Only ropivacaine at 7.5 mg/mL produced sufficient anesthesia. The onset of pulpal anesthesia occurred less than 10 minutes after injection and lasted for 2 to 6 hours. Pinprick anesthesia lasted for 3 to 6 hours and numbness of the lower lip lasted for 5 to 9 hours. CONCLUSION: This study shows that ropivacaine could be useful as a local anesthetic for mandibular nerve block in dentistry and that the very long duration of both pulpal and soft tissue anesthesia may be favorable in reducing postoperative pain.

Adolescent↗

An anatomical study of the cutaneous branches of the mental nerve.

Minor surgical procedures to the inner (mucosal) aspect of the lower lip may occasionally cause numbness of the overlying skin. This study was designed to find, by means of dissection and computerized three-dimensional reconstruction, why surgical interference with nerve fibres in the deep aspect of the lip can cause neurological deficit in the superficial layers. Thirteen cadaveric lips were examined by dissection under a surgical microscope (9 lips) or serial sectioning and computerized three-dimensional reconstruction (4 lips). Muscle mass, minor labial salivary glands and nerve fibres were identified and traced. Three patterns of mental nerve distribution were seen on dissection and two on computerized reconstruction; these latter corresponded to two of the patterns seen on dissection. Fibres passing close to the labial minor salivary gland mass were seen to travel towards the superficial aspect of the lip, terminating in the dermis. It is clear that there is no safe anatomical space for minor surgical procedures to the inner (mucosal) aspect of the lower lip if avoidance of cutaneous numbness is an important consideration. However, we describe a technique that may minimize the possibility of cutaneous numbness.

Aged↗

[Horner's syndrome following lumbar epidural anaesthesia--subdural block?].

A 28 year old primipara (37th gestational week) was scheduled to undergo delivery by caesarean section under epidural anaesthesia. An epidural catheter was easily inserted in the L3/L4 interspace. After a negative aspiration test 5 ml of bupivacaine 0.25% plus adrenaline 1:200,000 were injected and five minutes later 2 x 5 ml of bupivacaine 0.5% plus fentanyl 0.005 mg/ml were given. Ten minutes after the test dose the patient reported warmth and paraesthesia in the right leg and pelvis and numbness in the right periorbital region. The catheter was drawn back 1.5 centimeters and the operation could be performed under regional anaesthesia with supplemental doses of bupivacaine. Sensory level at the end of the operation was Th 4 which decreased continuously in the following two hours. Ocular symptoms (miosis, ptosis, right-sided numbness) as well as numbness in the right hand and leg persisted four hours longer. The most probable explanation for this peripheral Horner's syndrome is a subdural blockade caused by the first bupivacaine doses. The only known prophylaxis is a fractioned epidural injection of local anaesthetics.

Adult↗

[Idiopathic hypertrophic cranial pachymeningitis].

BACKGROUND: Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a chronic inflammatory disease of unknown origin that is morphologically characterized by a local fibrotic thickening of the dura mater with a sterile lymphocytic infiltrate. Patients usually present with chronic headache, ataxia and cranial nerve palsies. Because of the great diversity of symptoms and the fact that IHCP can be associated with many other disorders, there is often a long time between the occurrence of clinical features and making the diagnosis. During this time symptoms can further increase. In addition, this is the third case report describing bone involvement in this disorder. CASE REPORT: In May 2000, a 51-year-old woman presented with reduced visual acuity on both eyes, complete palsies of the fourth and sixth cranial nerve, a partial palsy of the third cranial nerve and numbness and pain concerning the area of the fifth cranial nerve on the left side, painful eye movement on the left side, headache, and numbness and palsies on the left side of her body. Magnetic resonance imaging of the brain showed a focal gadolinium-enhanced small thickening of the dura mater close to the left hemisphere and a homogeneous bone thickening in the same area close to the thickened dura mater. Cerebrospinal fluid analysis revealed an elevated cell count (lymphocytic pleocytosis), routine blood counts and serum chemistry showed an elevated white blood count, an elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Therapy with corticosteroids resulted in a complete remission in November 2000 except for a persistent numbness of the left side of her face and body and reduced visual acuity on both sides. The following three years were characterized by repeated clinical deteriorations followed by a temporary increase of the daily steroid dose. Altogether, daily oral steroid therapy could slow down the progression of disease and improve the visual acuity when compared with the first examination. CONCLUSIONS: Chronic headache, ataxia and cranial nerve palsies in combination with inflammation and dural thickening should call to mind idiopathic hypertrophic cranial pachymeningitis. In principle, every ophthalmological or neurological symptom can be associated with IHCP.

Cranial Nerve Diseases↗

Dual roles for the trimeric G protein Go in asymmetric cell division in Drosophila.

During asymmetric division, a cell polarizes and differentially distributes components to its opposite ends. The subsequent division differentially segregates the two component pools to the daughters, which thereby inherit different developmental directives. In Drosophila sensory organ precursor cells, the localization of Numb protein to the cell's anterior cortex is a key patterning event and is achieved by the combined action of many proteins, including Pins, which itself is localized anteriorly. Here, a role is described for the trimeric G protein Go in the anterior localization of Numb and daughter cell fate specification. Go is shown to interact with Pins. In addition to a role in recruiting Numb to an asymmetric location in the cell's cortex, Go transduces a signal from the Frizzled receptor that directs the position in which the complex forms. Thus, Go likely integrates the signaling that directs the formation of the complex with the signaling that directs where the complex forms.

Animals↗

Bazooka is required for localization of determinants and controlling proliferation in the sensory organ precursor cell lineage in Drosophila.

Asymmetric divisions with two different division orientations follow different polarity cues for the asymmetric segregation of determinants in the sensory organ precursor (SOP) lineage. The first asymmetric division depends on frizzled function and has the mitotic spindle of the pI cell in the epithelium oriented along the anterior-posterior axis, giving rise to pIIa and pIIb, which divide in different orientations. Only the pIIb division resembles neuroblast division in daughter-size asymmetry, spindle orientation along the apical-basal axis, basal Numb localization, and requirement for inscuteable function. Because the PDZ domain protein Bazooka is required for spindle orientation and basal localization of Numb in neuroblasts, we wondered whether Bazooka plays a similar role in the pIIb in the SOP lineage. Surprisingly, Bazooka controls asymmetric localization of the Numb-anchoring protein Pon, but not spindle orientation, in pI and all subsequent divisions. Bazooka also regulates cell proliferation in the SOP lineage; loss of bazooka function results in supernumerary cell divisions and apoptotic cell death.

Animals↗

Ergonomic problems associated with laparoscopy.

PURPOSE: Failure to understand the ergonomics of laparoscopic surgery has a potential to pose health problems for the surgeons. This study was planned to assess the prevalence, significance, and awareness of ergonomic problems associated with laparoscopy. MATERIAL AND METHODS: A questionnaire designed to assess the frequency and degree of physical discomfort practicing surgeons experienced and their awareness of the responsible factors was distributed to approximately 350 attendees of the Live International Workshop and CME on Laparoscopic Urologic Surgery. The response sheets were analyzed. RESULTS: Two hundred four attendees completed the questionnaire, of whom 131 were performing laparoscopic surgery (Group A). The rest (N = 73) were practicing only conventional surgery (Group B). The correct answer to the pictorial question, which tested the correct grip technique, was 81% and 56% in Group A and B, respectively (P = 0.0003). Group A surgeons were significantly (P = 0.04) better at answering the questions on neurapraxia. There was a statistically significant (P = 0.004) increase in the frequency of finger numbness and eye strain in Group A surgeons compared with Group B. Within Group A, finger numbness (P = 0.03) and eye strain (P = 0.002) were significantly greater in the junior laparoscopic surgeons than in senior laparoscopic surgeons. Surgeons having <2 years of laparoscopic surgical experience were significantly more affected. CONCLUSIONS: Surgeons performing laparoscopy have significant ergonomic problems, especially finger numbness and eye strain. Junior laparoscopic surgeons and surgeons with <2 years of laparoscopic surgical experience are more affected.

Adult↗

Regulation of membrane localization of Sanpodo by lethal giant larvae and neuralized in asymmetrically dividing cells of Drosophila sensory organs.

In Drosophila, asymmetric division occurs during proliferation of neural precursors of the central and peripheral nervous system (PNS), where a membrane-associated protein, Numb, is asymmetrically localized during cell division and is segregated to one of the two daughter cells (the pIIb cell) after mitosis. numb has been shown genetically to function as an antagonist of Notch signaling and also as a negative regulator of the membrane localization of Sanpodo, a four-pass transmembrane protein required for Notch signaling during asymmetric cell division in the CNS. Previously, we identified lethal giant larvae (lgl) as a gene required for numb-mediated inhibition of Notch in the adult PNS. In this study we show that Sanpodo is expressed in asymmetrically dividing precursor cells of the PNS and that Sanpodo internalization in the pIIb cell is dependent cytoskeletally associated Lgl. Lgl specifically regulates internalization of Sanpodo, likely through endocytosis, but is not required for the endocytosis Delta, which is a required step in the Notch-mediated cell fate decision during asymmetric cell division. Conversely, the E3 ubiquitin ligase neuralized is required for both Delta endocytosis and the internalization of Sanpodo. This study identifies a hitherto unreported role for Lgl as a regulator of Sanpodo during asymmetric cell division in the adult PNS.

Animals↗

Anatomic distribution of sensory symptoms in the hand and their relation to neck pain, psychosocial variables, and occupational activities.

To explore whether different distributions of numbness and tingling in the hand can be usefully distinguished in epidemiologic studies of disorders such as carpal tunnel syndrome, the authors used a postal questionnaire, an interview, and a physical examination to collect information about risk factors, symptoms, and signs from a general population sample of 2,142 adults in Southampton, England, during 1998-2000. The authors distinguished six distributions of numbness and tingling and compared their associations with other clinical findings and with known risk factors for upper limb disorders. Distinctive relations were found for symptoms that involved most of the palmar surface of the first three digits but not the dorsum of the hand or the little finger. Such symptoms were more often associated with positive Phalen's and Tinel's tests and, unlike other categories of sensory disturbance, were not related to neck pain or restriction of neck movement. They also differed in showing no association with lower vitality or poorer mental health but an association with repeated wrist and finger movements at work. These findings suggest that, in the classification of numbness and tingling of the hand, it may be useful to distinguish symptoms that involve most of the sensory distribution of the median nerve but not other parts of the hand.

Adult↗

Intravenous infusion of phenytoin relieves neuropathic pain: a randomized, double-blinded, placebo-controlled, crossover study.

UNLABELLED: Neuropathic pain responds inconsistently to opioids and nonsteroidal antiinflammatory drugs. However, oral anticonvulsants have a proven analgesic effect on neuropathic pain, but may not be practical in an acute flare-up. Phenytoin was the first oral anticonvulsant used as an analgesic for neuropathic pain. There have been few studies on the parenteral analgesic effect of this drug. In this randomized, double-blind, placebo-controlled, crossover study of 20 patients with acute flare-ups of neuropathic pain, we compared a 2-h placebo infusion with a 2-h infusion of 15 mg/kg phenytoin. Overall pain, shooting pain, burning pain, paresthesia, numbness, and sensitivity were measured using a 10-cm linear visual analog score. Numbness and sensitivity were reduced in the placebo group during infusion, but not in the 7 days after infusion. In the phenytoin group, there were significant reductions in burning pain (P < 0.05), shooting pain (P < 0.001), sensitivity (P < 0.001), numbness (P < 0.05), and overall pain (P < 0.005) during the infusion period. The reduction in overall pain persisted for 1 day, in sensitivity for 2 days, and in shooting pain for 4 days after infusion. We conclude that IV infusion of 15 mg/kg phenytoin has an analgesic effect in acute flare-ups of neuropathic pain and that this relief outlives both the infusion time and plasma half-life of phenytoin. IMPLICATIONS: Oral phenytoin can relieve neuropathic pain. The aim of this study was to examine the effect of IV phenytoin on neuropathic pain. The results indicate that IV phenytoin may be used to treat flare-ups of chronic neuropathic pain.

Adult↗