Muscle atrophy in muscle-specific tyrosine kinase (MuSK)-related myasthenia gravis

Myasthenia gravis (MG) with muscle-specific tyrosine kinase (MuSK) antibody (MuSK-MG) is often associated with prominent facial and bulbar muscle atrophy. It remains unclear whether the muscle atrophy is a consequence of long-term corticosteroid treatment, or of the disease process per se. Herein, we report a steroid-naive patient with MuSK-MG who presented with severe weakness and marked atrophy of the facial and tongue muscles.     

Clinical comparison of muscle-specific tyrosine kinase (MuSK) antibody-positive and -negative myasthenic patients

We assayed cryopreserved sera from 38 acetylcholine receptor (AChR) antibody-negative patients with myasthenia gravis (MG) who were followed clinically for muscle-specific tyrosine kinase (MuSK) antibodies and analyzed and compared their clinical characteristics. None of 13 sera from patients with purely ocular MG were positive. Sera from 10 of 25 patients (40%) with generalized MG were positive for MuSK antibodies. The age at onset of myasthenic symptoms was significantly earlier in MuSK antibody-positive patients (P = 0.02). MuSK antibodies were present in AChR antibody-negative patients of either gender, with virtually identical prevalence in women (41.2%) and men (37.5%). The distribution of weakness more commonly involved neck muscles in MuSK antibody-positive patients, and limb muscles in MuSK antibody-negative patients. Patients responded to immunosuppressive treatment regardless of whether MuSK antibody was present. We conclude that MuSK antibodies are present and diagnostically useful in a subset of myasthenic patients without AChR antibodies. Although the distribution of weakness differs somewhat depending on whether MuSK antibodies are present, responses to anticholinesterase and immunosuppressive treatments are similar.     

Prolonged improvement after rituximab: two cases of resistant muscle-specific receptor tyrosine kinase + myasthenia gravis

Forty percent to 50% of acetylcholine receptor antibody-seronegative patients with myasthenia gravis have muscle-specific receptor tyrosine kinase antibodies. Many muscle-specific receptor tyrosine kinase + myasthenia gravis patients remain refractory with conventional therapies. Rituximab is an anti-CD20 monoclonal antibody used in refractory B-cell disorders. Currently there is no standard dosing schedule for rituximab. We present two muscle-specific receptor tyrosine kinase + myasthenia gravis patients clinically refractory to conventional therapy who, after a single course of rituximab, became asymptomatic and discontinued all medication.     

Myasthenia gravis induced in mice by immunization with the recombinant extracellular domain of rat muscle-specific kinase (MuSK)

Myasthenia gravis (MG) is mostly caused by anti-acetylcholine receptor (AChR) auto-antibodies (Abs). Such Abs are undetectable in 10-15% of MG patients, but many have anti-muscle-specific kinase (MuSK) Abs. We injected recombinant rat-MuSK extracellular domain in H-2(a), H-2(b), H-2(bm12) and H-2(d) mice. Certain strains exhibited exercise-induced fatigue, tremors, weight loss, and some died after 2-3 injections. Compound muscle action potentials showed decrement with low-frequency repetitive nerve stimulation. Miniature endplate potentials decreased, suggesting lower numbers of endplates functional AChRs. Myasthenic sera inhibited agrin-induced AChR aggregation in C2C12 myotubes. Conclusion: Anti-MuSK Abs induce MG, which might also result from blocking the agrin-signaling pathway.     

Antibodies against Wnt receptor of muscle-specific tyrosine kinase in myasthenia gravis

Muscle-specific tyrosine kinase (MuSK) antibodies are detected in a proportion of myasthenia gravis (MG) patients who are negative for acetylcholine receptor (AChR) antibodies and have prominent bulbar weakness and crises. In the MuSK ectodomains, the immunoglobulin-like 1 and 2 domains (Ig1/2) mediate the agrin–Lrp4–MuSK signaling and the cysteine-rich domain (CRD) mediates the Wnt–MuSK–Dishevelled signaling; both contribute to AChR clustering. Immunoblotting against recombinant proteins showed MuSK Ig1/2 antibodies in 33 anti-AChR-negative MG patients; 10 patients of them (30%) were additionally positive for MuSK CRD antibodies. The result suggests that MuSK antibodies have heterogeneity in their binding to functional domains of MuSK.     

Oculocerebrocutaneous (Delleman) syndrome: report of two cases

We describe two cases of oculocerebrocutaneous syndrome (OCCS) or Delleman syndrome, characterized by congenital anomalies that involve the skin, orbit, and central nervous system (CNS). Complete MRI studies of the orbit, CNS and the entire spinal region must be performed in these cases. New MRI techniques can show cortical malformations, such as polymicrogyria, lissencephaly, or abnormal disposition of cortical sulci and gyri. Lesions can be bilateral or unilateral, as occurred in our patients. In one case, the ocular, skin, cerebral, and cerebellar lesions involved mainly the same side, whereas in the second case, all anomalies were generalized and the patient also showed skin hypopigmented lesions distributed bilaterally. Both patients show severe encephalopathy and Dandy-Walker malformation. One case is blind and shows generalized hydrocephalus, and the other one has vision through an eye, and has complete agenesis of the corpus callosum and severe disorder of neuronal migration and cortical organization with polymicrogyria and abnormal cortical sulci and gyri in a cerebral hemisphere. Our second case shows arachnoid cysts in both temporal, retrocerebellar, and spinal (D(8)-D(11)) regions, and lipoma in the pontomedullary and spinal (D(4)-D(7)) regions. The latter features correspond more to ECCL than to OCCS. The overlap between the two syndromes is unquestionable and it is possible that they constitute different manifestations of the same disorder.     

Massive creatine kinase elevations with quetiapine: report of two cases

Massive elevations of serum creatine kinase (CK) can occur in a significant number of patients treated with neuroleptics in the absence of neuroleptic malignant syndrome (NMS). We report two cases of CK-elevations associated with quetiapine treatment, which disappeared after drug discontinuation. To our knowledge, case number one is the first case of quetiapine-induced CK elevation in a neuroleptic-na?ve patient. We thus suggest CK assessment when myalgia occurs with neuroleptic treatment.     

Titer of anti-muscle-specific receptor tyrosine kinase (MuSK) antibody correlated with symptomatic improvement in response to corticosteroid therapy in a patient with anti-MuSK antibody-positive myasthenia gravis: a case report]

A 54-year-old woman was admitted to our hospital because of diplopia, dysphagia, dropped head, and muscle weakness with easy fatigability. A neurological examination showed bilateral ptosis, ocular motility disorder, dysphagia, and weakness of the neck extensor muscles. Edrophonium and repetitive nerve stimulation tests of the thenar muscles showed positive results. The serum titer of anti-acetylcholine receptor antibody was negative. A thymoma was not detected in her chest CT. Finally, she was diagnosed with anti-MuSK antibody-positive myasthenia gravis based on the high serum titer of anti-MuSK antibody (239 nmol/l). Her symptoms improved after administration of prednisolone. However, the symptoms were aggravated when the prednisolone dosage was reduced, and the titer of anti-MuSK antibody rose at the same time. We evaluated the possible association between changes in the severity of her clinical symptoms and the titer of the antibody during prednisolone therapy. It was revealed that the titer of the antibody was correlated to the severity of clinical symptoms expressed by a QMG (Quantitative Myasthenia Gravis) score. These findings indicate that monitoring the titer of anti-MuSK antibody can be useful for assessing disease activity as well as decision making during treatment.     

软腭震颤(附2例临床报道)

软腭震颤(palatal tremor)是一种罕见独特的疾病,是以软腭快速、节律性、不随意运动构成的障碍,既往曾称腭肌阵挛(palatal myoclonus).现报道2例并复习文献如下.     

心肺复苏后肌阵挛(附2例临床报告)

目的:探讨心肺复苏后肌阵挛的分类、诊断、治疗原则及预后。方法:报道两例心肺复苏后肌阵挛病例并综合已有的文献研究。结果:两例分别明确诊断为急性症状性肌阵挛和慢性症状性肌阵挛,并根据其不同的病理生理机制,给予相应的治疗,两例均存活且临床症状得到控制。结论:心肺复苏后肌阵挛应根据不同的分类及病理生理机制,采取有针对性的措施控制症状,并尽快改善中枢神经系统缺血缺氧损伤,合并癫痫与否对于治疗及预后有参考意义。     

Familial form of Fahr syndrome (report of two cases)

Two cases of familial form (in brothers) of extensive, symmetric, idiopathic calcifications of the basal ganglia and cerebellum (Fahr syndrome) are described. In discussion of factors predisposing to appearance of such idiopathic calcifications, particular attention was given to meningoencephalitis suffered in childhood and coexistence of a tumour of the sella of prolactinoma type, in case 1. Attention was also called to progressive, copious clinical and radiological symptology of the discussed cases. It was impossible to suggest a probable type of inheritance (parents of the patients were dead).     

Medullomyoblastoma: report of two cases

Two cases of medullomyoblastoma in children are described. The muscular component showed different features in the two cases and were associated with neuronal differentiation. Morphological, immunohistochemical, and electron microscopical findings are presented. The origin of the muscular component is discussed in relation to the findings in other cases of the literature. Both differentiation from primitive neuroepithelial cells and derivation from ectomesenchyme are considered.     

Motor neglect of thalamic origin: report on two cases (author's transl)

Two cases of thalamic lesions with motor neglect are presented. The syndrome of motor neglect was complete in those cases with a) underutilization of left limbs, but good utilization upon verbal orders, b) loss of placement reaction, c) weakness of movement when hand was approaching the target, d) weakness of motor reaction to nociceptive stimuli. Those cases confirm that motor neglect exists after thalamic lesions and bring pathologic clues for topographic discussion. Motor neglect seems to be a particular case of partial unilateral neglect throwing some doubt on the hypothesis of a global trouble of hemispheric activation. Prevalence of left motor neglects suggests some linkage between propositional motility and language. One may suppose that in the right hemisphere language is able to have a vicarious action when spontaneous activation is lost; at the opposite, in the left hemisphere language and motility would be too linked to let this dissociation be generally possible.     

手-口综合征二例报告

1914年Sitting报告了手-口综合征(cheiro-oral syndrome,COS)。近年虽有散在报告，仍属罕见，笔者接诊2例,现报告如下。     

Central neurocytoma: report of two cases

INTRODUCTION: Central neurocytomas are rare neuroectodermal tumors believed to arise from the subependymal matrix of the lateral ventricles. CASE REPORTS: A 26-year-old woman and a 33-year-old man each had a large, heterogeneous, contrast enhancing mass in the lateral ventricles at the foramen of Monro causing bilateral hydrocephalus. The woman died after surgery, but the man is asymptomatic after three years. HISTOPATHOLOGY: Both tumors were composed of isomorphic rounded cells positive for synaptophysin, chromogranin and NSE, while some reacted for GFAP, vimentin and S-100 protein. Electron microscopy revealed neuropil-like tissue between cells, but synapses were rare.     

Slipped clip: report of two cases

Aneurysm rest occurs in 1 to 10% of operated patients and of these, 21.8% are due to slipped clips. D'Angelo and coworker (1998) found 1 to 10% of residual aneurysms. They suggest that if the residual aneurysm has less than 2 mm, angiographic control must be performed after 3-5 years of the surgical procedure; if between 2 and 4 mm, the angiographic control must be done in the first 6 months after surgery and then, anually. If it has more than 4mm a direct surgical approach is advised. We present the cases of two female patients submitted to microsurgical treatment of intracranial aneurysm, without any intra-operative abnormal event. The angiographic study further made showed displacement of the clip from its original position and aneurysm again. A review of the literature is also presented.     

Chordoid meningioma: report of two cases

We present CT scan, MRI and histopathologic findings of two patients harboring a rare type of meningioma. In the first case, a 52 year-old male patient, a large parasellar mass invading the cavernous sinus, infiltrating the infratemporal fossa and extending as low as C2 was founded. The tumor was isointense on T1, enhanced strongly with gadolinium injection, and was hyperintense on T2. In the second case, a 19-year-old male patient, a large high density temporal right mass was disclosed by CT scan. Both patients were taken to surgery. In the first case, only a partial removal was possible to be accomplished due to a severe intra operative bleeding. In the second case, the tumor was totally removed. Both showed characteristic pathologic findings of a meningioma resembling a chordoma. Meningioma is a relatively common intracranial tumor, occurring most frequently in adults, showing a wide variety of growth patterns. We described a pattern that had a peculiar chordoma-like appearance. The pathological findings and the differential diagnosis from chordoma are discussed.     

Bannwarth syndrome: report of two cases

Report of two cases of Bannwarth syndrome, an apparently neglected condition both in the Italian and in the English literature.