No healing improvement after rotator cuff reconstruction augmented with an autologous periosteal flap.

PURPOSE: To show descriptive clinical and magnetic resonance (MR) imaging results after an additional periosteal flap augmentation in mini-open rotator cuff reconstruction and to evaluate potential healing improvement at long-term follow-up. METHODS: Twenty-three patients with degenerative rotator cuff tears were followed after receiving a mini-open single-row repair with a subtendinous periosteal flap augmentation. Data were collected preoperatively, after 12 months and after 11 years. Clinical examination, simple shoulder test (SST), Constant-Murley Score (CS), ultrasonography examination and 3T MR imaging were performed. RESULTS: Out of 23 patients, 20 were available for short-term and 19 for final follow-up at a median of 11.5 years (range 10.4-13.0). Questions answered with "yes" in SST improved from baseline 5.0 (range 1.0-8.0) to short 10.5 (range 8.0-12.0) and final follow-up 12.0 (range 7.0-12.0). CS improved from 53.5 (range 25.0-66.0) to 80.8 (range 75.9-89.3) and finally to 79.8 points (range 42.3-95.4). Improvement was highly significant (p < 0.05). Severe retears were found in 9/19 patients. Ossifications along the refixed tendon were noticed in 8/19 cases. Ossifications did not correlate with clinical outcome. At final follow-up, patients with retears seemed likely to have lower strength values in CS (mean ± SD) than patients without retears (7.3 ± 4.1 vs. 12.8 ± 5.3; p < 0.05). CONCLUSION: No positive effect on improving healing response in rotator cuff refixation with a periosteal flap augmentation could be found. Retear rate is comparable to that of conventional rotator cuff refixation in the published literature. Ossifications along the tendon, without negatively affecting the clinical outcome, were seen. This invasive technique cannot be advised and should not be used anymore. LEVEL OF EVIDENCE: IV.

[Surgical treatment of posterosuperior impingement (PSI)]. / Operative Therapie des posterosuperioren Impingements (PSI).

OBJECTIVE: To restore the physiologic anterior and posterior capsular volume to achieve an anatomic central contact point of the glenohumeral articulation and treatment of concomitant glenohumeral injuries due to posterosuperior impingement (PSI). INDICATIONS: Plateauing of clinical improvement despite adequate nonsurgical treatment (for at least 6-12 months). CONTRAINDICATIONS: General contraindications for elective arthroscopic surgery. SURGICAL TECHNIQUE: Diagnostic arthroscopy of the glenohumeral joint through the posterior portal to assess stability of the biceps-labral complex even in the Abduction and External Rotation (ABER) position to confirm the diagnosis of PSI and to detect concomitant glenohumeral injuries. In most cases posterosuperior SLAP (superior labrum anterior posterior) repair or tenodesis of the long head of the biceps. POSTOPERATIVE MANAGEMENT: Arm sling for 6 weeks with limited range of motion. Free active range of motion of elbow and wrist. Limited shoulder external rotation for 6 weeks. Free shoulder range of motion from week 7, full daily life activities after 12 weeks. Modification of the postoperative management according to intraoperative findings. RESULTS: At our hospital 18 overhead athletes (6 women, 12 men, mean age 31 years) with PSI without SLAP lesion or rotator cuff tear underwent isolated plication of the anteroinferior capsule after primary nonsurgical treatment. At a mean period of 9 months, 16 patients returned to their pre-injury sports activity level, 2 patients had to give up their sports due to persisting shoulder problems. At a mean follow-up of 27 months (range 12-55 months) the Walch Duplay score was on average 82.9 ± 8.3 for men and 73.8 ± 5.9 for women.

Stem cells and bFGF in tendon healing: Effects of lentiviral gene transfer and long-term follow-up in a rat Achilles tendon defect model.

BACKGROUND: The influence of stem cells and lentiviral expression of basic fibroblastic growth factor (bFGF) on tendon healing and remodelling was investigated in an in-vivo long-term (12 weeks) rat Achilles tendon defect model. METHODS: In sixty male Lewis rats, complete tendon defects (2.4 mm) were created and either left untreated (PBS) or treated by injection of stem cells lentivirally expressing the enhanced green fluorescence marker gene eGFP (MSC-LV-eGFP) or basic fibroblast growth factor bFGF (MSC-LV-bFGF). Tendons were harvested after 12 weeks and underwent biomechanical and (immuno)-histological analysis. RESULTS: After 12 weeks the mean ultimate load to failure ratio (treated side to contralateral side) in biomechanical testing reached 97 % in the bFGF-group, 103 % in the eGFP-group and 112 % in the PBS-group. Also in the stiffness testing both MSC groups did not reach the results of the PBS group. Histologically, the MSC groups did not show better results than the control group. There were clusters of ossifications found in all groups. In immunohistology, only the staining collagen-type-I was strongly increased in both MSC groups in comparison to PBS control group. However, there were no significant differences in the (immuno)-histological results between both stem cell groups. CONCLUSION: The biomechanical and (immuno)-histological results did not show positive effects of the MSC groups on tendon remodelling in a long-term follow-up. Interestingly, in later stages stem cells had hardly any effects on biomechanical results. This study inspires a critical and reflected use of stem cells in tendon healing.

Stem cells and basic fibroblast growth factor failed to improve tendon healing: an in vivo study using lentiviral gene transfer in a rat model.

BACKGROUND: The aim of this controlled study was to investigate the influence of mesenchymal stem cells (MSCs) and lentiviral (LV) expression of basic fibroblast growth factor (bFGF) on tendon remodeling in an in vivo rat model of an Achilles tendon defect. METHODS: In eighty-four male Lewis rats, complete 2.4-mm tendon defects were created and were either left untreated (the phosphate-buffered saline solution [PBS] group) or were treated with mesenchymal stem cells expressing enhanced green fluorescent protein (the MSC-LV-eGFP group) or with mesenchymal stem cells expressing basic fibroblast growth factor lentivirally (the MSC-LV-bFGF group). After fourteen and twenty-eight days, the tendons were harvested and analyzed biomechanically and immunohistologically. RESULTS: After fourteen days, both mesenchymal stem cell groups were slightly superior in biomechanical testing. However, only the PBS control group showed a significant increase in biomechanical results over time (fourteen versus twenty-eight days; p = 0.012). Biomechanical results were better after twenty-eight days for the control group than for both MSC groups. However, the difference was significant only with regard to the stiffness results in the comparison of the PBS control and the eGFP stem cell group (p = 0.024). Histologically, the MSC groups had no better results than the control group after fourteen and twenty-eight days. In immunohistology, only labeling for type-I procollagen was strongly increased in both MSC groups in comparison with the PBS control group (p = 0.0009 for the MSC-LV-bFGF group and p = 0.0041 for the MSC-LV-eGFP group at fourteen days, and p = 0.004 and p = 0.132, respectively, at twenty-eight days). There were no significant differences in the immunohistological results between the stem cell groups. CONCLUSIONS: The biomechanical and immunohistological results showed that mesenchymal stem cells in both groups had only partially positive effects on tendon remodeling in the initial stages; however, in later stages, stem cells had potentially negative effects on biomechanical results. The additional expression of bFGF in stem cells had negligible effects on tendon remodeling. CLINICAL RELEVANCE: Preliminary studies using stem cells are partially promising; however, there are no relevant clinical data showing that stem cells are of significant benefit. The present study should lead to a more critical evaluation and thoughtful use of stem cells in humans until more clinical data are available.

[Latissimus dorsi transfer for the treatment of irreparable rotator tears: indication, surgical technique, and modifications]. / Latissimus-dorsi-Transfer bei nichtrekonstruierbarem Rotatorenmanschettendefekt : Indikation, Operationstechnik und Technikmodifikationen.

OBJECTIVE: Improvement of glenohumeral dynamic centering and active external rotation by a transfer of the latissimus dorsi tendon to the greater tuberosity or the lateral proximal humerus. INDICATIONS: Irreparable posterosuperior rotator cuff tears. CONTRAINDICATIONS: Cuff tear arthropathy, subscapularis tendon tear, deltoid insufficiency, palsy of the axillary nerve. SURGICAL TECHNIQUE: Diagnostic arthroscopy in lateral decubitus position. Placement of suture through the biceps tendon and supragleonidal tenotomy. Posterior approach. Preparation and mobilization of a pedicled latissimus dorsi flap. Second anterior incision with delta split. Debridement of the torn rotator cuff. Insertion of suture anchors in the greater tuberosity. Passing of the muscle flap inferior to the posterior deltoid and fixation with suture anchors to the greater tuberosity (where applicable suturing with remaining rotator cuff tissue). POSTOPERATIVE MANAGEMENT: Immobilization in a thorax abduction cast for 6 weeks. Passive exercises out of the cast (IR/ER 0-0-free and ABD/ADD free-45-0°). Active assistive exercises from week 4 postoperatively. Stepwise increase of passive range of motion from week 7. Unlimited active range of motion from week 10. RESULTS: After an average follow-up of 57.6 (SD 27.5) months 17 patients were examined clinically. The average age at time of surgery was 55.6 (SD 7.7) years. At follow-up the patients showed an average Constant score of 64.4 points (SD 17.4). The active external rotation in 0° abduction was 16° (SD 17). The 4 patients (23%) with a sonographically-detected retear of the latissimus flap presented worse clinical results.

[Arthroscopic options for regenerative treatment of cartilage defects in the shoulder]. / Arthroskopische Möglichkeiten biorekonstruktiver Verfahren bei Knorpelschäden der Schulter.

Chondral or osteochondral lesions of the shoulder may lead to premature osteoarthritis of the glenohumeral joint as regeneration of damaged articular cartilage is lacking. Rising health awareness, increasingly active populations and improvements in medical techniques have increased the application of cartilage regenerative minimally invasive approaches for glenohumeral joint preservation or delayed prosthetic replacement. In contrast to the conclusive and mostly convincing mid-term results of cartilage regenerative techniques known for the knee, clinical results of innovative therapeutic approaches with glenohumeral cartilage defects are more or less absent. Current techniques include procedures for mesenchymal stem cell recruitment, such as microfracturing, (autologous) osteochondral transplantation, (matrix-associated) autologous chondrocyte transplantation and biological resurfacing, addressing focal chondral defects up to massive structural osteochondral defects. With increasing arthroscopic applicability, they evolve to important tools in the armamentarium of the shoulder surgeon. Future clinical data will determine evidence-based applicability, enabling standardized treatment selection.

[May eccentric training be effective in the conservative treatment of chronic supraspinatus tendinopathies? A review of the current literature]. / Kann exzentrisches Training in der konservativen Therapie von chronischen Supraspinatus-Tendinopathien effektiv sein? Eine Übersicht zur aktuellen Literatur.

Eccentric training (ET) has been shown to be an effective conservative treatment option for chronic patellar and Achilles tendinopathies. As part of the four-muscle-tendon-complex of the rotator cuff, the supraspinatus is involved most commonly in shoulder disorders. Histopathologic alterations of the supraspinatus tendon are comparable to findings in lower extremity tendinopathies. Hence, the question arises whether the concept of eccentric training can be successfully transferred to the upper extremity. Yet, no randomised controlled trials have been published to support this theory. This problem emerges from the fact that the supraspinatus is part of a complex functional unit. Consequently, surrounding soft tissues are frequently concomitantly affected. The inherent etiology and genesis of pathologic alterations in the supraspinatus tendon and its influence on shoulder disorders is not clear to date. However, the apparent success of ET in managing tendinopathies of the lower extremity urges further scientific work for developing evidence-based guidelines for the conservative treatment of tendinopathies in the shoulder region. Taking into account this lack of data as well as the anatomical and functional constraints, the aim of this work is to review the current state of the literature.

Clinical and structural evaluation of arthroscopic double-row suture-bridge rotator cuff repair: early results of a novel technique.

PURPOSE: Assessment of repair integrity and clinical outcome after arthroscopic repair of rotator cuff tears in double-row suture-bridge technique with the use of a new knotless suture-anchor system. METHODS: The first treated 25 patients with arthroscopic rotator cuff repair in the suture-bridge technique using a novel knotless anchor and chain-link suture system were evaluated. Patients with isolated full-thickness supraspinatus tears were selected. They were followed clinically with functional scores (Constant score, ASES index), visual analog scale (VAS), and instrumentally with Isobex digital strength analyzer preoperatively, at 6 and 14 months postoperatively. The repair integrity was evaluated with MRI at an average of 14 months postoperatively. RESULTS: Significant improvement of pain, strength, range of motion, and functional scores occurred (P < 0.05). There was a re-tear rate of 20%. The subjective parameters (VAS and ASES Index) showed non-significant (n.s.) differences between the re-tear and intact repair groups, whereas the objective parameters (Constant score, muscle power and active ROM) showed significant differences between both groups (P < 0.05). CONCLUSION: The functional outcome has improved significantly with this new knotless anchor-chain system and was more superior in shoulders with intact repair, whereas the resulted repair integrity was not better than other types of double-row repair techniques mentioned in the recent literature. However, this early report of the novel technique may show limited power for comparison due to the relatively small sample size.

[Latissimus dorsi transfer--comparison of results after primary and revision surgery: a retrospective matched-pair analysis]. / Zeigt der Latissimus-dorsi-Transfer als Revisionsoperationvergleichbare Ergebnisse zum Primäreingriff? Eine retrospektive Matched-Pair-Analyse

AIM: Latissimus dorsi transfer (LdT) has been proposed for the treatment of irreparable rotator cuff tears of the infra- and supraspinatus. The purpose of this retrospective study was to evaluate the results of latissimus dorsi transfer in revision surgery in comparison to primary surgery. METHOD: Between 1998 and 2005 a group of 124 patients has been treated with a latissimus dorsi transfer. From this group 34 patients (Group 1 = revision LdT n = 17, Group 2 = primary LdT n = 17)were examined in a retrospective matched-pair study after an average follow-up of 20 months (Group 1) and 28 months (Group 2) by clinical examination and X-ray. Functional results were assessed with use of the age- and gender-matched Constant Score (CS). RESULTS: The age- and gender-matched Constant Score increased significantly in both groups from preoperatively 51% in Group 1 and 57% in Group 2 up to a postoperative score of 73% in Group 1 and 84% in Group 2 (p = 0.001/p = 0.007). By comparison of the 2 groups there is a significantly higher postoperative age- and gender-matched Constant Score for Group 2 (p = 0.03). Active ROM showed postoperatively no significant difference (Abd/Flex p = 0.8). The Hornblower sign is significantly more frequently positive in Group 1(p < 0.001). The comparison of arthroscopically and open previous surgery for the subgroups of revision latissimus dorsi transfer shows a trend for an increased postoperative age- and gender-matched Constant Score in the arthroscopic group (82%/69% p = 0.06) with a preoperative CS of 50%/52% (p = 0.9). There is no significant difference in the incidence of postoperative complications. CONCLUSION: Considering the correct indication for latissimus dorsi transfer there is no difference for reduction of pain and active ROM between primary and revision surgery. But the revision cases show a significantly lower age- and gender-matched Constant Score and a higher incidence of a positive Hornblower sign. A higher risk of postoperative complications for the revision group could not be found. In summary, the latissimus dorsi transfer was of significant benefit for both groups and we can also recommend this technique for revision surgery.

[Allografts for cruciate ligament reconstruction]. / Allogene Kreuzbandtransplantation.

Allografts have an essential significance in the surgical reconstruction of ligamentous injuries around the knee joint. While in primary anterior cruciate ligament reconstruction allografts are less important than autografts, at least in the European countries, the usage of allografts in anterior cruciate ligament revision surgery is increasing. In addition, allografts represent a good alternative for the reconstruction of the posterior cruciate ligament and the posterolateral structures. Especially in multiligament reconstructions of the knee joint, the usage of allografts may prevent iatrogenic damage of the already traumatized periarticular soft tissue. The present article focuses on the application and clinical results of allografts for ligament reconstruction around the knee joint. Furthermore, the immunological and biological principles of tendon allografts, their availability, processing, and security are discussed.

Activity of asynchronous flight muscle from two bee families during sonication (buzzing).

The indirect flight muscles of bees are used to produce a variety of actions in addition to flight, including sonication, which has a higher frequency than flight. We observed the dynamic movement of the scutum during sonication and the transition from tethered flight to sonication. During sonication, the scutum oscillated above its rest position, indicating that the conformation of the structural components of the thorax had been altered. Sonication vibrations of the thorax occurred by deformation of the scutum rather than by opening of the scutal fissure and are smaller than vibrations associated with flight. During tethered flight, the ratio of muscle activity (recorded via electromyograms) between the dorsal longitudinal muscles and the dorsoventral muscles approached 1, but during sonication the ratio was significantly higher (up to 4.0). This increase may cause the dorsal longitudinal muscles to contract further than the dorsoventral muscles and close the scutal fissure during sonication, so limiting the displacement of the wings and 'decoupling' them from the indirect flight muscles.

Ciprokiren (Ro 44-9375). A renin inhibitor with increasing effects on chronic treatment.

The present study characterizes the new transition-state renin inhibitor ciprokiren (Ro 44-9375) in squirrel monkeys. Arterial blood pressure was monitored by telemetry in freely moving, chronically instrumented conscious animals. In vitro at pH 7.4, ciprokiren inhibited human renin in buffer and human plasma with an IC50 of 0.07 and 0.65 nmol/L, respectively. It was equipotent against primate plasma renin and also inhibited plasma renin from dog and guinea pig in the nanomolar range (IC50, 29 and 65 nmol/L, respectively). After acute oral administration it reduced arterial blood pressure dose dependently in normotensive sodium-depleted and cyclosporin-induced hypertensive squirrel monkeys, starting with the minimal oral dose of 3 micrograms/kg. Daily oral doses of 1 microgram/kg showed a progressive blood pressure decrease, with a maximal response reached after 1 week. The drug could also be applied transdermally with similar hemodynamic effects without any decrease of plasma renin activity or plasma immunoreactive angiotensin II. Thus, ciprokiren is characterized in squirrel monkeys as a renin inhibitor with high in vivo potency that might act mainly in the tissular compartment.

[Vitamin K deficiency with erythromycin. Observation of a boy treated with valproate]. / Vitamin K-Mangel unter Erythromycin. Beobachtung bei einem mit Valproat behandelten Jungen.

A nine year old boy had been treated with valproic acid during one and a half years because of a grand mal epilepsy. Under an additional medication with erythromycin succinate syrup this patient developed a deficiency of prothrombin-complex, which was reversible immediately after oral intake of vitamin K. In this case it is assumed that the simultaneous application of both valproic acid and erythromycin succinate seems to suppress the vitamin K producing intestinal tract bacteria, which has not been reported in the literature so far.

Identification of thoracic gland constituents from maleXylocopa spp. latreille (Hymenoptera: Anthophoridae) from arizona.

Some male carpenter bees (Xylocopa spp.) possess massive propodeal exocrine glands that produce copious quantities of multicomponent blends of lipoidal material. Some of these compounds are volatile, producing a "flowery" aroma that can be easily detected several meters downwind from a territorial male. Chemical characterization of these secretions showed them to be blends of terpenoid compounds or fatty acid derivatives. InX. varipuncta, the mixture is composed of alltrans-geranylgeraniol, alltrans-farnesal, and an isomer of 3,7, 11-trimethyl-2,7,10-dodecatrienal in an approximate 9∶6∶1 ratio. The secretion ofX. micheneri contains isopropyl oleate, (Z)-11-eicosen-1-ol, oleyl alcohol, and methyl palmitate at approximately 63∶24∶11∶1. We hypothesize that these compounds act as pheromones that aid in attracting and holding conspecific females to symbolic nonresource encounter sites where mating occurs. They also appear to have utility as chemotaxonomic markers at the subgeneric level.

[Homozygous infant in a family with hereditary protein C deficiency]. / Homozygoter Säugling in einer Sippe mit erblichem Protein C-Mangel.

We report on a female infant homozygous for protein C deficiency in a Jordanian family with frequent intermarriage. A protein C antigen of 0.6% was determined. The parents first noticed painful nodular indurations in subcutanous tissue as well as blue-red skin coloration at the age of 6 months. The girl repeatedly suffered from microthrombotic events in parts of the body with large areas of subcutaneous fat. In contrast, the numerous heterozygous carriers with partial protein C deficiency did not show an increased tendency to thrombosis. From the history an autosomal-recessive inheritance may be inferred. Other authors reporting on homozygous cases also postulate the presence of a recessive gene. It is of interest that the infant described here differs from those in other case reports in the age at manifestation of the disease. The homozygous infant showed the first symptoms as late as the age of 6 months, whereas other case reports describe severe symptoms immediately after birth. All symptoms of disease were treated successfully with prothrombin complex concentrate without additional heparin protection. Microthrombotic events subsided quickly, and a large ulcer in the left flank healed almost completely within 6 days.

Aggressive combination chemotherapy of bone marrow relapse in childhood acute lymphoblastic leukemia containing aclacinomycin-A: a multicentric trial.

An intensive 7-day combination chemotherapy protocol was designed to reinduce children with early bone marrow relapse of acute lymphoblastic leukemia (less than 6 months after the end of or during preceding treatment). This aggressive approach seemed to be justified for a group of patients who were at the highest risk for ultimate treatment failure. In all, 38 children were enrolled for study. The ratio of male (median age, 10 years) to female (median age, 13 years) subjects was 27:11. Thirty patients were treated for their first relapse and eight for their second or subsequent relapse. Isolated bone marrow involvement was present in 24 cases. All patients had received heavy pretreatment including anthracyclines with cumulative doses of between 120 and 240 mg/m2. 22 of these patients, achieved complete remission, ten did not respond to therapy, and six died from the toxicity of the protocol. Cardiac failure was the cause of death in one child (after additional radiotherapy for a mediastinal mass). No further clinical manifestation of cardiomyopathy could be observed. The other five patients died from hemorrhages or infectious complications. The main side effects were fever, gastrointestinal problems, stomatitis, and severe bone marrow aplasia lasting for about 2 weeks with nadirs of platelets and white blood count around days 10-14. The remission rate of 60% was acceptable, though not satisfactory. Only four children survived disease-free for 13+, 14+, 20+, and 22+ months after diagnosis of relapse.

[Successful chemotherapy in a primary cerebral centroblastic non-Hodgkin's lymphoma in childhood]. / Erfolgreiche Chemotherapie bei einem primär zerebralen zentroblastischen Non-Hodgkin-Lymphom im Kindesalter.

Primary lymphomas of the central nervous system (CNS) are rare diseases. Often these tumors are surrounded by glia cells and may, therefore, be misdiagnosed as 'astrocytomas' with accompanying reactive lymphocytosis. A 15-year old patient was irradiated to the posterior cranial fossa and the brain stem because of a supposed astrocytoma. Five months after completion of radiotherapy he presented two lesions each in the right and left cerebral hemisphere. Repeated biopsy led to a revision of the primary diagnosis in favor of a B-cell Non-Hodgkin lymphoma (centroblastic type). After cyclic polychemotherapy including high-dose methotrexate and cytosine-arabinoside he entered a complete remission. No further radiotherapy was given. So far, 18 months after discontinuating therapy, the patient has been in complete remission and is in an excellent physical condition.

[Biclonal leukemia O-ALL/AMoL) with 11;19 translocation and trisomy X in an 8-month-old girl]. / Biklonale Leukämie (O-ALL/AMoL) mit 11;19 Translokation und Trisomie X bei einem 8 Monate alten Mädchen.

Biclonal leukemia was diagnosed in an 8 months old girl, combining lymphoblastic (FAB L1) and monoblastic (FAB M 5) phenotypes which were classified as O-ALL and AMol by immunological examination of surface-antigens. Chemotherapy for one cell type resulted in predominance or relapse of the other one. Chromosomal abnormalities diagnosed in the lymphoblastic clone consisted of translocation t(11;19)(q23;p13) and triple X. The breakpoint 11q23 neighbouring one well known oncogene (ets) is not strictly associated with special leukemic phenotypes. But it is often found in infants and usually correlated with a poor prognosis. The data of 18 patients with hybrid leukemias registered in the BFM studies strongly support the fatal course of the disease. 12 months after diagnosis approximately 1 out of 10 children is expected to survive disease-free.

[Malignant melanoma in the child--2 case reports]. / Malignes Melanom beim Kind--2 Fallberichte.

Case histories of two infants with malignant melanoma are presented. Both tumors had developed from a congenital mole to advanced disease with lymph node metastasis at time of diagnosis, findings which are commonly correlated with poor outcome. Initially, both patients were surgically treated. From the experience with few described cases of melanoma in childhood and with a large number of adult patients, neither chemotherapy and conventional BCG immunotherapy nor irradiation seem to be an effective treatment and are accompanied by many adverse side effects. Therefore in one patient therapy was limited to surgery alone. In the other child it was followed by treatment with high-dose recombinant alpha-2-interferon (1 Mill. i.u./Kg X d) plus an H2-receptor antagonist. Unexpectedly this girl developed neurological side effects, characterized by spastic paraparesis, indicating damage to the first motoneuron. All symptoms completely resolved after discontinuation of drugs within three months. Both children have been in complete remission for 18+ and 32+ months, respectively.