Patient autoantibodies deplete postsynaptic muscle-specific kinase leading to disassembly of the ACh receptor scaffold and myasthenia gravis in mice.

The postsynaptic muscle-specific kinase (MuSK) coordinates formation of the neuromuscular junction (NMJ) during embryonic development. Here we have studied the effects of MuSK autoantibodies upon the NMJ in adult mice. Daily injections of IgG from four MuSK autoantibody-positive myasthenia gravis patients (MuSK IgG; 45 mg day(1)i.p. for 14 days) caused reductions in postsynaptic ACh receptor (AChR) packing as assessed by fluorescence resonance energy transfer (FRET). IgG from the patients with the highest titres of MuSK autoantibodies caused large (51-73%) reductions in postsynaptic MuSK staining (cf. control mice; P < 0.01) and muscle weakness. Among mice injected for 14 days with control and MuSK patient IgGs, the residual level of MuSK correlated with the degree of impairment of postsynaptic AChR packing. However, the loss of postsynaptic MuSK preceded this impairment of postsynaptic AChR. When added to cultured C2 muscle cells the MuSK autoantibodies caused tyrosine phosphorylation of MuSK and the AChR beta-subunit, and internalization of MuSK from the plasma membrane. The results suggest a pathogenic mechanism in which MuSK autoantibodies rapidly deplete MuSK from the postsynaptic membrane leading to progressive dispersal of postsynaptic AChRs. Moreover, maintenance of postsynaptic AChR packing at the adult NMJ would appear to depend upon physical engagement of MuSK with the AChR scaffold, notwithstanding activation of the MuSK-rapsyn system of AChR clustering.

Chorea induced by non-ketotic hyperglycaemia: a case report.

We describe an 81-year-old woman presenting with sudden onset of generalised chorea. She was unaware of suffering from diabetes. Laboratory screening revealed non-ketotic hyperglycaemia. Brain magnetic resonance imaging (MRI) failed to show basal ganglia abnormalities. Monotherapy with subcutaneous regular insulin induced a progressive normalisation of glycaemia as well as a parallel improvement of the abnormal involuntary movement scale on a nine-day sequential observation. This correlation strongly supports the hypothesis that non-ketotic hyperglycaemia itself might play a major pathogenetic role in chorea associated with non-ketotic hyperglycaemia. Diabetes mellitus should be suspected in patients who develop sudden onset of chorea even in the absence of putaminal abnormalities on MRI.

Prevention of recurrent radicular pain after lumbar disc surgery: a prospective study.

BACKGROUND: Postoperative epidural fibrosis is a major causative factor of low-back pain even if microsurgical techniques are adopted to reduce this phenomenon. To prevent the recurrent radicular pain caused by this problem, we utilized adipose tissue drawn from the same patient; at the end of surgical procedure, the fat was placed around the spinal root or the dural sac. This procedure was evaluated by a prospective, randomised study. METHOD: From 180 patients operated on for lumbar discectomy between January 2000 to December 2001, 74 were enclosed in the study. In 37 patients, the spinal root was covered by autologous fat (group A), in the other 37 (control group, B), this procedure was not adopted. One year after surgery, all the patients were evaluated with clinical and radiological (Magnetic Resonance Imaging) follow-up. Only two patients were lost to follow-up. FINDINGS: 71% of the patients in group A had 100% of clinical and radiological post-operative outcome score; this result was obtained only in 35% of the patients in group B. A clinical score evaluating pain syndrome (from grade 0 to 5) and a radiological score evaluating postoperative fibrosis (from grade 0 to 4) was adopted. Therefore, group A had best outcome as compared to control group. CONCLUSIONS: The authors found a positive effect in the reconstruction of epidural fat with autograft of adipose tissue to prevent postoperative scarring and failed-back syndrome related to postoperative fibrosis.

Anterior submuscular transposition of the ulnar nerve in severe cubital tunnel syndrome. Personal experience.

AIM: The authors report the results of anterior submuscular transposition, on a clinical series of selected patients with severe cubital tunnel syndrome. In these patients, the degree of ulnar nerve compression was valued using a grading system that includes measurements of motor and sensitive function. In this series, a technique of flexor-pronator mass Z-lengthening was adopted. METHODS: From 1998 to 2002, 18 patients were surgically treated with anterior deep submuscular transposition for cubital tunnel syndrome. The preoperative status was determined using Dellon's classification. Fifteen out of 18 patients were graded as Dellon's grade 3 (severe syndrome). The mean duration of follow-up after surgery was 27.6 months. RESULTS: Postoperative outcome was assessed in all the 15 patients according to a modified Bishop scoring system. Based on this score, 6 patients (40%) were graded as excellent, 7 (47%) were graded as good and 2 (13%) were graded as fair. The complete recovery occurred about 6 months after surgery. None complication was observed. CONCLUSION: Treatment of severe cubital syndrome by means of a technique of flexor-pronator mass Z-lengthening was linked to 87% rate of good to excellent results. The present study demonstrate the feasibility of this technique with restitutio ad integrum in spite of the severity of the syndrome. None failure nor recurrence was present in this series.

Does the neuronal plasticity exist in elderly patients? report of an unusual clinical case.

STUDY DESIGN: Case report. OBJECTIVE: To report complete recovery after paraplegia in an elderly patient after removal of meningioma at C7-T1 level. SETTING: Department of Neurosurgery, Reggio Calabria, Italy. METHODS: An 82-year-old lady with 48 months of progressive weakness and numbness was admitted with complete paraplegia lasting 15 days. Investigations (magnetic resonance imaging (MRI)) demonstrated a meningioma at C7-T1. The tumour compressed the extremely thinned spinal cord. MRI after surgery showed no evidence of residual tumour and the spinal cord was of normal dimensions. The patient recovered fully and locomotion was restored. CONCLUSION: Surgical decompression gave an excellent result. The result raises the possibility of neuronal plasticity.

"Approaches and surgical results in the treatment of ventral thoracic meningiomas. Review of our experience with a postero-lateral combined transpedicular-transarticular approach.".

BACKGROUND: The surgical treatment of anterior thoracic meningiomas provides a set of technical difficulties: the access is obstructed by the spinal cord posteriorly, thoracic cage and musculature laterally, mediastinum and pleural cavity anteriorly. It is fundamental to avoid any manipulation of the compressed, but also undamaged spinal cord: this shows significant plastic capabilities. Any effort should be directed to maximizing the contribution of the plasticity in order to obtain a good functional recovery. METHOD: We have utilized a postero-lateral combined transpedicular-transarticular approach in order to obtain less invasiveness on the neural structures. Ten patients with ventral thoracic meningioma were operated in the last 5 years. The preoperative clinical evaluation, follow-up monitoring, timing of recovery, Clinical/Functional Grade change were analysed. FINDINGS: 8 Patients had significant neurological improvement, 2 were unchanged. Magnetic Resonance Imaging (MRI) was useful in preoperative planning. Radical excision was possible in all patients and the late postoperative MRI did not reveal recurrence of the lesions at this time. To date, there has been no evidence of clinical or radiological instability. INTERPRETATION: We found this surgical exposure very helpful in the treatment of anterior thoracic meningiomas. The related morbidity and risk of instability are minimal. The combined postero-lateral approach offers a good surgical access to ventral, lateral and dorsal aspects of the thoracic spinal canal without manipulation of the spinal cord. Exposure is obtained by avoiding damage to the pleura and manipulation of the lungs and mediastinum and may be a feasible alternative in elderly patients, too.

Oral squamous cell carcinoma: a retrospective study of 740 cases in a Brazilian population.

The purpose of this study was to evaluate, retrospectively, the profile of patients with oral squamous cell carcinoma. They were referred to two hospitals of Belo Horizonte (MG, Brazil) between 1986 and 1996. The medical records of 740 patients presenting oral squamous cell carcinoma were reviewed in detail. The TNM classification and staging, age, gender, race, occupation, and site of the primary tumor were recorded. The male-to-female ratio was 4.8:1. The mean age was 58.6 years. Most of the patients were in their sixties and were farm workers. The tumors were found principally on the tongue. There was a close relationship between some habits (tobacco and alcohol consumption) and the development of oral squamous cell carcinoma. Most of the patients sought medical care in the first year, even though almost half of them had lesions in stage T4. The identification of the characteristics of this specific population might reflect either accomplishments or problems in oral cancer control and can enable the development of a primary prevention program for oral squamous cell carcinoma.

Primary cervical melanoma with brain metastases. Case report and review of the literature.

Primary intramedullary melanoma is a very rare tumor that occurs most frequently in the middle or lower thoracic spinal cord. The authors present a case of primary cervical cord melanoma that developed in a 62-year-old man who was surgically treated and subsequently underwent radiation therapy. Clinical and histogenetic features of this neoplasm and results of chemo-. radio-, and immunotherapy are reported. Both "dysembryogenetic" and "mesodermal" hypotheses on the origin of primary spinal melanoma are discussed.