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PubMed1995

A 55-year-old man with bilateral lower-limb numbness and weakness.

The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to orthopedic surgeons. The initial history, physical findings, and roentgenographic examinations appear on this page. The clinical and roentgenographic diagnoses are presented on the following pages.

Cauda Equina↗
PubMed1996

Numb & number.

Explore the source record for details and available documents.

Anesthesia, Dental↗
PubMed1997

Only a subset of the binary cell fate decisions mediated by Numb/Notch signaling in Drosophila sensory organ lineage requires Suppressor of Hairless.

In Drosophila, an adult external sensory organ (bristle) consists of four distinct cells which arise from a sensory organ precursor cell via two rounds of asymmetric divisions. The sensory organ precursor cell first divides to generate two secondary precursor cells, IIa and IIb. The IIa cell then divides to produce the hair cell and the socket cell. Shortly after, the IIb cell divides to generate the neuron and the sheath cell. The membrane-associated protein Numb has been shown to be required for the first two asymmetric divisions. We now report that a new hypomorphic numb mutant not only displays a double-socket phenotype, due to a hair cell to socket cell transformation, but also a double-sheath phenotype, due to a neuron to sheath cell transformation. This provides direct evidence that numb functions in the neuron/sheath cell lineage as well. Those results, together with our observation from immunofluorescence analysis that Numb forms a crescent in the dividing IIa and IIb cells suggest that asymmetric localization of Numb is important for the cell fate determination in all three asymmetric cell divisions in the sensory organ lineage. Interestingly, we found that in the hair/socket cell lineage but not the neuron/sheath cell lineage, a Suppressor of Hairless mutation acts as a dominant suppressor of numb mutations whereas Hairless mutations act as enhancers of numb. Moreover, epistasis analysis indicates that Suppressor of Hairless acts downstream of numb, and results from in vitro binding analysis suggest that the genetic interaction between numb and Hairless may occur through direct protein-protein interaction. These studies reveal that Suppressor of Hairless is required for only a subset of the asymmetric divisions that depend on the function of numb and Notch.

Animals↗
PubMed2000

Gamma knife radiosurgery for trigeminal neuralgia: the initial experience of The Barrow Neurological Institute.

PURPOSE: To assess the efficacy and complications of Gamma Knife radiosurgery for trigeminal neuralgia. METHODS AND MATERIALS: The Barrow Neurological Institute (BNI) Gamma Knife facility has been operational since March 17, 1997. A total of 557 patients have been treated, 89 for trigeminal neuralgia (TN). This report includes the first 54 TN patients with follow-up exceeding 3 months. Patients were treated with Gamma Knife stereotactic radiosurgery (RS) in uniform fashion according to two sequential protocols. The first 41 patients received 35 Gy prescribed to the 50% isodose via a single 4-mm isocenter targeting the ipsilateral trigeminal nerve adjacent to the pons. The dose was increased to 40 Gy for the remaining 13 patients; however, the other parameters were unvaried. Outcome was evaluated by each patient using a standardized questionnaire. Pain before and after RS was scored as level I-IV per our newly-developed BNI pain intensity scoring criteria (I: no pain; II: occasional pain, not requiring medication; III: some pain, controlled with medication; IV: some pain, not controlled with medication; V: severe pain/no pain relief). Complications, limited to mild facial numbness, were similarly graded by a BNI scoring system. RESULTS: Among our 54 TN patients, 52 experienced pain relief, BNI score I in 19 (35%), II in 3 (6%), III in 26 (48%), and IV in 4 (7%). Two patients (4%) reported no relief (BNI score V). Median follow-up was 12 months (range 3-28). Median time to onset of pain relief was 15 days (range 0-192), and to maximal relief 63 days (range 0-253). Seventeen (31%) noted immediate improvement (</= 24 h). Prior to RS, all patients were on pharmacologic therapy felt to be optimal or maximal. Twenty-two (41%) were able to stop medications entirely (BNI score I or II). Another 16 (30%), with BNI Score III relief, decreased medication intake by at least 50%. Patients with classical TN pain symptoms were more likely to stop medications than those with atypical features, 49% (21 of 43) versus 9% (1 of 11). This difference was significant at p = 0.040. Statistically, the finding most predictive for pain relief was new facial numbness following RS. Each of the 5 patients with new numbness after RS developed BNI score I relief, contrasting with 35% for the 49 patients with no new numbness (p = 0.019). Complications have been limited to delayed, mild facial sensory loss. Before RS, 17 patients had numbness from prior invasive procedures, none of whom reported a worse numbness score after treatment. Thirty-seven patients had no facial numbness at the time of RS, of whom 5 developed facial hypesthesia. Each rated this as "mild, not bothersome." There have been no other sequellae. CONCLUSION: RS is an effective treatment, and is the least invasive nonpharmacologic therapy for TN. It carries a small risk of mild facial hypesthesia, a side effect which, somewhat ironically, may be desirable, because it appears to correlate favorably with an excellent pain response. We currently include radiosurgery among the appropriate options for TN patients who have failed optimal medical management, with or without prior invasive neurosurgical procedures. We present here BNI scoring systems for pain intensity and facial numbness. These have proved simple and reliable, have facilitated data collection, rendered analysis more objective, and improved our ability to discuss results with patients and colleagues.

Adult↗
PubMed2004

Gamma knife surgery for trigeminal neuralgia: outcome, imaging, and brainstem correlates.

PURPOSE: To review our results with gamma knife surgery (GKS) in the treatment of trigeminal neuralgia (TN), and to determine whether pain relief, medication usage, and the development of facial numbness are affected by trigeminal nerve compression, MRI imaging quality, or brainstem radiation dose. METHODS AND MATERIALS: One hundred twelve patients with TN refractory to medical or surgical management were treated at the University of Maryland Gamma Knife Center between June 1996 and July 2001. Patients were treated using a 4-mm shot to the trigeminal nerve, at a point 2-4 mm anterior to the root entry zone of the nerve into the pons. The median dose prescribed was 75 Gy (range, 60-80 Gy). T1- and T2-weighted, axial, 1.5-mm-thick MRI images were obtained using three-dimensional gradient echo acquisition after contrast injection for treatment planning. MRI images were evaluated for imaging quality (i.e., the adequacy of visualization of the affected prepontine trigeminal nerve), the presence of trigeminal nerve compression, and the brainstem dose. Follow-up data were obtained via telephone interviews, and patients were asked to rate their pre-GKS and post-GKS pain using the Barrow Neurological Institute (BNI) Pain Intensity Scale. Patients were also asked about side effects from GKS and were asked to rate any facial numbness on the BNI Facial Numbness Scale. Medication use, time to pain response, and duration of relief were also evaluated. RESULTS: Ninety-six patients who had follow-up data were included in the analysis. Eighty-six patients (89.6%) responded to GKS with an improvement in BNI pain class. Ten patients (10.4%) were found to have an MRI of poor quality, 30 (31.3%) fair quality, and 56 (58.3%) good quality. Forty-two (43.8%) received 10% of the maximal dose to the brainstem edge, whereas 54 (56.2%) received 20%. Eleven (11.5%) patients were found to have obvious nerve compression by MRI. Imaging quality (p = 0.1863), presence of compression (p = 0.1147), and brainstem dose (p = 0.3168) did not correlate with treatment response. There was also no correlation between these variables (MRI quality, compression, and brainstem dose) and medication use (p = 0.5372, p = 0.0913, p = 0.6832, respectively). Facial numbness was the only side effect experienced. Thirteen patients reported varying degrees of facial numbness, but there was no correlation between imaging quality (p = 0.0600), brainstem dose (p = 0.6773), and presence of compression (p = 0.5785) with the development of facial numbness. CONCLUSIONS: Gamma knife surgery is effective in the treatment of TN and has a favorable side effect profile. Treatment response and the development of facial numbness do not correlate with MRI imaging quality, presence of nerve compression, or radiation dose to the brainstem.

Adult↗
PubMed2002

Drosophila Aurora-A is required for centrosome maturation and actin-dependent asymmetric protein localization during mitosis.

BACKGROUND: During asymmetric cell division in the Drosophila nervous system, Numb segregates into one of two daughter cells where it is required for the establishment of the correct cell fate. Numb is uniformly cortical in interphase, but in late prophase, the protein concentrates in the cortical area overlying one of two centrosomes in an actin/myosin-dependent manner. What triggers the asymmetric localization of Numb at the onset of mitosis is unclear. RESULTS: We show here that the mitotic kinase Aurora-A is required for the asymmetric localization of Numb. In Drosophila sensory organ precursor (SOP) cells mutant for the aurora-A allele aurA(37), Numb is uniformly localized around the cell cortex during mitosis and segregates into both daughter cells, leading to cell fate transformations in the SOP lineage. aurA(37) mutant cells also fail to recruit Centrosomin (Cnn) and gamma-Tubulin to centrosomes during mitosis, leading to spindle morphology defects. However, Numb still localizes asymmetrically in cnn mutants or after disruption of microtubules, indicating that there are two independent functions for Aurora-A in centrosome maturation and asymmetric protein localization during mitosis. Using photobleaching of a GFP-Aurora fusion protein, we show that two rapidly exchanging pools of Aurora-A are present in the cytoplasm and at the centrosome and might carry out these two functions. CONCLUSIONS: Our results suggest that activation of the Aurora-A kinase at the onset of mitosis is required for the actin-dependent asymmetric localization of Numb. Aurora-A is also involved in centrosome maturation and spindle assembly, indicating that it regulates both actin- and microtubule-dependent processes in mitotic cells.

Actins↗
PubMed2003

A retrospective audit of long-term lower limb complications following leg vein harvesting for coronary artery bypass grafting.

OBJECTIVE: To evaluate the prevalence of leg complications following leg-vein harvest for coronary artery bypass grafting. METHOD: A questionnaire was sent to patients who had coronary artery bypass surgery between January 1993 and December 1998. Questions addressed pain, numbness, infection, swelling and general healing. The relationship between the risk factors of diabetes, peripheral vascular disease, previous fractures/injuries to legs, previous deep vein clots and arthritis affecting the legs with post operative symptoms of pain, numbness, swelling and general healing was explored with multivariate analysis. RESULTS: Of 700 questionnaires sent out 497 were returned, of which 422 (60%) were suitable for analysis. Numbness or tingling related to the wound was reported by 256 (61%), of whom 94 (37%) improved within 3 months. However, 105 (41%) had persistent numbness beyond 2 years. Pain in the wound was reported by 193 (46%), of whom 149 (77%) reported that this had improved by 3 months and only 19 (10%) had pain persisting beyond 2 years. A leg wound infection was reported by 126 (32%) patients, with 82 (65%) of these receiving antibiotics. A total of 336 (87% of 387 responses) described their wound as completely healed at 3 months. Unilateral leg swelling was reported by 175 (41%) with 98 of these (56% of those with swelling) improving by 3 months and 41 (23%) with swelling persisting beyond 2 years. There was no relation of wound problems to examined risk factors diabetes (P-values for numbness 0.31, wound healing 0.15, swelling 0.21, pain 0.22) and peripheral vascular disease (P-values for numbness 0.8, wound healing 0.21, swelling 0.18, pain 0.09). There was insufficient data to comment on the influence of fractures/injuries to legs, previous deep vein clots and arthritis affecting the legs. CONCLUSIONS: Wound complications are common following leg vein harvest. Prevalence of infection was higher than has previously been reported. Few people suffer long-term pain from saphenous nerve damage although paraesthesia and swelling were common long-term complications. We did not identify either diabetes or peripheral vascular disease as a risk factor for pain, numbness, swelling or problems with general healing. There is a need for a large multicentre prospective study.

Adult↗
PubMed2002

Comparison of side effects between sentinel lymph node and axillary lymph node dissection for breast cancer.

BACKGROUND: Axillary lymph node dissection (ALND) is often associated with permanent arm side effects. Side effects after sentinel lymph node dissection (SLND) should be less common, because the surgery is less extensive. METHODS: The study compared side effects and interference with daily life between 169 women who underwent an SLND and 78 who underwent an ALND for breast cancer. Patients rated symptom severity and interference with daily life caused by pain, numbness, limitation of arm range of motion (ROM), and arm swelling at 1, 6, and 12 months after surgery by using the Measure of Arm Symptom Survey. Repeated-measures and regression analyses for each time period were used to determine associations between symptoms and dissection type. RESULTS: At 1 month, SLND patients reported less pain, numbness, limitation in ROM, and seromas than ALND patients. At 6 months, SLND patients had less pain, numbness, and arm swelling, and at 12 months, SLND patients had less numbness, arm swelling, and limitation in ROM than ALND patients. At 1 month, pain, numbness, and limitation in ROM interfered significantly more with daily life for ALND patients. At 6 and 12 months, only numbness interfered more with daily life for ALND patients. CONCLUSIONS: SLND was associated with fewer side effects than ALND at all time points.

Adult↗
PubMed2006

Hand-arm vibration syndrome with use of anti-vibration chain saws: 19-year follow-up study of forestry workers.

OBJECTIVES: Hand-arm vibration syndrome (HAVS) consists of vascular and neurological component. Musculoskeletal component has not been delineated yet. In the present follow-up study, we evaluated the prevalence of HAVS and the cumulative exposure to vibration among a cohort of forestry workers. Special interest was given to numbness and musculoskeletal disorders of upper extremity and neck in forestry workers. METHODS: A follow-up study starting from 1976 was conducted among forestry workers in Suomussalmi in Finland. Total exposure of hand-arm vibration was recorded during 11 cross-sectional surveys. The last study was carried out in 1995. The lifetime dose of vibration energy was calculated. A cohort of 52 forest workers participated to all 11 cross-sectional surveys 1976-1995. HAVS and musculoskeletal disorders were evaluated. RESULTS: The prevalence of active vibration white finger (VWF) decreased from 13 to 4% in the cross-sectional study. In the cohort VWF decreased from 17 to 8% and numbness increased from 23 to 40%. Rotator cuff syndrome (P=0.034) and epicondylitis (P=0.004) associated with numbness. Regional neck pain was diagnosed in 38% of workers and associated with low back pain. In modeling VWF, the lifelong vibration energy (OR 1.03, CI 1.01-1.05), and smoking (OR 7.36, CI 1.07-50.76) were significant. Numbness was modeled by pain in upper extremities (OR 12.43, CI 2.42-63.80) and neck pain (5.97, CI 1.25-28.39), not by lifelong vibration energy. Right rotator cuff syndrome was modeled by age (OR 2.58, CI 1.04-6.41) and lifelong vibration energy (OR 1.04, CI 1.00-1.07). CONCLUSIONS: The prevalence of VWF constantly decreased. Numbness did not follow the vibration exposure profile. Numbness also associated with upper extremity musculoskeletal disorders. Hand-arm vibration associated with the right rotator cuff syndrome in forestry workers.

Cohort Studies↗
PubMed2005

Quantitative analysis of protein dynamics during asymmetric cell division.

In dividing Drosophila sensory organ precursor (SOP) cells, the fate determinant Numb and its associated adaptor protein Pon localize asymmetrically and segregate into the anterior daughter cell, where Numb influences cell fate by repressing Notch signaling. Asymmetric localization of both proteins requires the protein kinase aPKC and its substrate Lethal (2) giant larvae (Lgl). Because both Numb and Pon localization require actin and myosin, lateral transport along the cell cortex has been proposed as a possible mechanism for their asymmetric distribution. Here, we use quantitative live analysis of GFP-Pon and Numb-GFP fluorescence and fluorescence recovery after photobleaching (FRAP) to characterize the dynamics of Numb and Pon localization during SOP division. We demonstrate that Numb and Pon rapidly exchange between a cytoplasmic pool and the cell cortex and that preferential recruitment from the cytoplasm is responsible for their asymmetric distribution during mitosis. Expression of a constitutively active form of aPKC impairs membrane recruitment of GFP-Pon. This defect can be rescued by coexpression of nonphosphorylatable Lgl, indicating that Lgl is the main target of aPKC. We propose that a high-affinity binding site is asymmetrically distributed by aPKC and Lgl and is responsible for asymmetric localization of cell-fate determinants during mitosis.

Animals↗
PubMed2005

Glycerol rhizotomy versus gamma knife radiosurgery for the treatment of trigeminal neuralgia: an analysis of patients treated at one institution.

BACKGROUND: Medically refractory trigeminal neuralgia (TN) has been treated with a variety of minimally invasive techniques, all of which have been compared with microvascular decompression. For patients not considered good surgical candidates, percutaneous retrogasserian glycerol rhizotomy (GR) and gamma knife (GK) radiosurgery are two minimally invasive techniques in common practice worldwide and used routinely at Jefferson Hospital for Neuroscience. Using a common pain scale outcomes questionnaire, we sought to analyze efficacies and morbidities of both treatments. METHODS AND MATERIALS: Between June 1994 and December 2002, 79 patients were treated with GR and 109 patients underwent GK for the treatment of TN. GR was performed with fluoroscopic guidance as an overnight inpatient procedure. GK was performed using a single 4-mm shot positioned at the root exit zone of the trigeminal nerve. Radiation doses of 70-90 Gy prescribed to the 100% isodose line were used. Treatment outcomes including pain response, pain recurrence, treatment failure, treatment-related side effects, and overall patient satisfaction with GK and GR were compared using a common outcomes scale. Using the Barrow Neurologic Institute pain scale, patients were asked to define their level of pain both before and after treatment: I, no pain and no pain medication required; I, occasional pain not requiring medication; IIIa, no pain and pain medication used; IIIb, some pain adequately controlled with medication; IV, some pain not adequately controlled with medication; and V, severe pain with no relief with medication. We used posttreatment scores of I, II, IIIa, and IIIb to identify treatment success, whereas scores of IV and V were considered treatment failure. Results were compiled from respondents and analyzed using SAS software. Statistical comparisons used log-rank test, univariate and multivariate logistic regression, Fisher's exact test, and Wilcoxon test with significance established at p < 0.05. RESULTS: There were 63 evaluable GK patients and 36 evaluable GR patients. The median follow-up time was 34 and 29 months for the GR and GK groups, respectively. The median age was 69 and 70 years and the median number of years with TN pain was 6 and 7 years in the GR and GK groups, respectively. Thirty-one GR (86%) and 58 GK (92%) patients achieved a successful treatment outcome (p = 0.49). The median time to pain relief was < or = 24 h in the GR group and 3 weeks in the GK group (p < 0.001, ordinal logistic regression). Nineteen GR and 26 GK patients experienced pain recurrence or pain never relieved (p = 0.30). The median time to pain recurrence was 5 and 8 months in the GR and GK groups, respectively (p = 0.22). At last follow-up, however, a statistically significant greater number of GR vs. GK patients had failed treatment. Twelve or 33% of GR patients, whereas 8 or 13% of GK patients, had BNI scores of 4 or 5 (p = 0.019, Fisher's exact test). When both initial and late treatment failures were combined, the overall rate of treatment failures was 39% in the GR group and 24% in the GK group (p = 0.023, log-rank). More GR patients developed facial numbness and facial numbness morbidity than GK patients: 19 GR (54%) and 17 GK patients (30%) developed new facial numbness and 12 GR and 7 GK patients reported either somewhat or very bothersome facial numbness (p = 0.018). On multivariate analysis, only treatment with GK and severity of pain before treatment significantly predicted treatment response. GK patients were more likely to have a lower pain score at last follow-up than were GR patients (p = 0.005, OR = 4.3), and patients with pretreatment pain scores of 5 were more likely to have lower posttreatment pain scores than patients with pretreatment pain scores of 4 and lower (p = 0.003, OR = 4.0). CONCLUSION: Despite greater facial numbness morbidity and a higher failure rate, GR provided more immediate pain relief than GK. GR therefore should be considered in patients with disabling trigeminal pain requiring urgent pain relief. For all other patients, GK provides better long-term pain relief with less treatment-related morbidity, and should therefore be considered the preferred treatment for patients with medically refractory trigeminal neuralgia who are not suitable candidates for microvascular nerve decompression.

Aged↗