Objective To investigate the clinical and pathological features of adult form nemaline myopathy. Methods Biopsied muscle specimens from two patients were observed using enzymatic histochemical method and electron microscope. Results These two patients were found with an initial onset from neck muscle weakness at the age of 52 and 36 years respectively, followed by trunk and limb muscle involvement to a variant degree. Type Ⅰ fiber atrophy and numerous granules (rod) were found in both patients in light microscopy. In case 1, the centralized nuclei were seen almost in all normal sized muscle fibers. Electron microscopic observation showed marked myofibril disorganization and numerous rod-like formations. Two inclusion-carrying nuclei were detected in case 1. The intranuclear inclusion showed a lattice pattern of Z-disc line or sarcoplasmic rod. Conclusions Adult form nemaline myopathy is clinically nonspecific. Rod-like structures might be found either in sarcoplasma or in nucleus. Centralized nuclei might coexist with rods in adult form nemaline myopathy. As compared to the child form, the adult one might often show a marked muscle fiber atrophy.

Objective To investigate the clinical and pathological features of pure type mitochondrial myopathy.Methods Clinical manifestations and pathological features of biopsied muscle specimens were summarized retrospectively in 9 cases of pure mitochondrial myopathy. 6 of them were followed up on the purpose of prognostic analysis.Results 9 cases of pure mitochondrial myopathy were clinical characterized by exclusive skeletal muscle involvement and fluctuating proximal muscle weakness. Extraocular muscles were spare. Most patients had moderately increased creatine phosphokinase level (539～2 913U/L). Electromyography examination showed myogenic changes in 6 cases and neurogenic in 3 cases. Pathologically, 8 cases had typical ragged red fibers (RRF) accounting for 5% to 60%. Mitochondrial intracristal inclusion bodies were observed by electron microscope in the patient with atypical RRF. Focal cytochrome C oxidase (COX) deficiency was seen in 4 cases and total deficiency in 2 cases. To a certain degree, the percentage of RRF was parallel to muscle weakness. Following-up data from 6 patients showed that symptoms had improved in 5 patients after treatment with vitamin B, vitamin E, CoQ 10 and inosine. One had a sudden death with unknown reason.Conclusion Pure mitochondrial myopathy may be a distinct subset of mitochondrial diseases that preferentially affects trunk and proximal muscles,Pathological charactoristic had typical RRF and COX deficiency,and RRF is related to patient's condition.It has relative chronic process and benign prognosis.

Objective To investigate the clinical and pathological features of riboflavin-reactive lipid storage myopathy.Methods Clinical material of 4 patients with riboflavin-reactive lipid storage myopathy were analyzed retrospectively.Results All the patients were subacute onset and presented proximal and axial muscle weakness accompanied by intolerance to excise.Amyotrophy and weakness involved in neck and paraspinal muscle were found in 3 cases,and chewing muscle weakness in 2 cases.Electromyogram showed myogenic changes in 2 cases and reduced conductive velocity of tibial nerves in 1 case.Muscle Biopsy study showed markedly increased lipid droplets in muscle fibers.The ragged red fibers,succinate dehydrogenase strongly reactive vessels and COX deficiency fibers which supported mitochondrial myopathy were not detected.Electromicroscope observation revealed that the structure and quantity of mitochondria were normal.All the patients had a dramatic response to riboflavin treatment.Two cases were cured and the other two were improved significantly.Two cases relapsed 1 year and 5 years later,respectively,and riboflavin was still effective for them.Conclusions Riboflavin-reactive lipid storage myopathy is a myopathy characterized by preferential involvement of neck,paraspinal and chewing muscles.The distinct pathological features are lipid accumulation in muscle fibers without any abnormalities of mitochondrial structure and quantity.Riboflavin alone is effective for this myopathy and this is distinguished from other myopathies.

Objective To investigate the clinical,genetic and pathological features of familial chronic progressive external ophthalmoplegia (CPEO) type of mitochondrial myopathy.Methods Clinical manifestations, family histories and pathological findings of 21 patients with CPEO type of mitochondrial myopathy from 3 families constellations were analyzed retrospectively.Results All the patients had ptosis and movement disorder of eyeball, with or without myasthenia. An autosomal dominant pattern of transmission was deduced from one family and a maternal transmission appeared most likely in the other two families. The striking and common pathologic findings were presence of ragged red fibers and cytochrome C oxidase (COX) deficiency fibers under microscope. Ultrastructural alterations included subsarcolemmal accumulation of mitochondria, increase of mitochondria with abnormal shape, disarrangement of cristae and paracrystaline inclusion bodies.Conclusions The clinical and pathological features between generations and families seem to be similar. It is suggested that different genetic mode of CPEO may lead to similar clinical and pathological features.

Objective To explore the clinical and pathological features of leprous neuritis.Methods Sural nerve biopsied specimens from one patient with leprous neuritis were analyzed with histopathology and electron microscopy.Results The main clinical characteristics included injuries of sensory nerves with numbness and pain in the distal limbs, vegetative nerve functional disturbance, and the asymmetrical bulky ulnar nerve. The pathological changes were the presence of lymphocytic infiltrates in the endoneurial and epineurial spaces, a mild stenosis of small vessel with a large number of perivascular lymphocytic and mononuclear phagocytic infiltrates combined with epithelioid cells form. Anti-acid staining demonstrated the positive leprosy bacillus in nerve fibers. A nearly completely loss of myelinated fibers and obvious connective tissue proliferation were also seen in the sural nerve. The electron microscopy observed marked axonal degeneration of unmyelinated nerve fibers with many leprosy bacillus in Schwann' cells. This case was treated with Aminophenylsulfone and Dehydrocortisone for one year and his condition had improved.Conclusions Diagnosis of leprous neuritis depends on the nerve biopsy, and the early treatment may relieve disability.

Objective To explore the clinical features of hyperthyroidism combined with Moyamoya disease. Methods The manifestations of clinic and neuroimaging in 4 patients with hyperthyroidism combined with Moyamoya disease were retrospectively analyzed.Results 4 patients were young or middle-aged females and onset of the disease were acute or subacute. 2 cases had the history of hyperthyroidism for 4 and 1 years and other 2 cases were diagnosed of hyperthyroidism in the duration of hospital stay. All of them presented with focal neurologic deficit(3 of motor weakness or fatigue in the limbs, 2 of facial paralysis and 2 of aphasia). All of them had thyromegaly Ⅰ?～Ⅱ? and 1 of them had vascular murmur in thyroid region.Thyroid function tests revealed thyrotoxicosis, the level of fT3 was 10.1～30.8 pmol/L,the level of fT4 was 17.9～154.8 pmol/L, the level of TSH was 0.01～0.1 mU/L.DSA or MRA showed stenosis or occlusion of the terminal portions of the bilateral or unilateral internal carotid arteries and abnormal vascular network in the vicinity of the arterial occlusion. The patients recovered after the anti-thyroid therapy and treatments for the cerebral stroke. Then ,15 ～ 60 months were followed up respectively, there was no relapsed of cerebral stroke in them. Conclusion Hyperthyroidism combined with Moyamoya disease is only seen in females. Cerebral stroke is occurred during the presence of thyrotoxicosis. Anti-thyroid treatment is beneficial for recovery of the centre nervous system and prevention of recurrence.

Objective To investigate the clinical and pathological features of distal myopathy with rimmed vacuoles(DMRV). Methods Clinical manifestations and pathological features of biopsied muscle specimens were summarized and analysed retrospectively. Muscle specimens were collected from biceps brachii (3 cases), tibialis anterior (2 cases), quadriceps femoris (1 case)and gastrocnemius (3 cases) respectively. 6 cases were observed by electronic microscope. Results The onset of disease was ranged in age from 15 to 33 years, averaging 25 years. It is more common in women than in men in a ratio of 2∶1. Distal muscle weakness and atrophy of the lower extremities was predominant in early stage. Varied involvement of proximal and trunk muscles, with sparing of the facial, extraocular, bulbar, intercostal and diaphragm muscles was recognized in the advanced stage. The striking and common pathologic finding was the presence of rimmed vacuoles in muscle fibers with little evidence of necrotic or regenerative processes. Electronic microscopic study showed an accumulation of myeloid structure in 5 cases, cytoplasmic inclusion bodies in 4 cases and intranuclear filamentous inclusions in 2 cases. A perforated nuclear envelope and extrusion of filaments in adjacent cytoplasm were found in an enlarged nucleus filled with tubulofilementous inclusion.Conclusion The clinical and pathological findings of DMRV occurred in China is basically similar to those reported by Japanese. Ultrastructural study suggested that sarcoplasmic filamentous inclusions might originate from perforated nuclei with inclusion body, which predicts that the rimmed vacuoles are likely to be the end products of nuclear disintegration and focal myofibrillar degeneration.

Objective:To analyze the clinical features, imaging findings and gene test of patients with type Ⅱ Alexander disease.Methods:All the clinical data of three cases with type Ⅱ Alexander disease from August 2018 to June 2020 in the Department of Neurology, Qilu Hospital of Shandong University (Qingdao) and Qilu Hospital of Shandong University were collected, and their clinical and imaging findings were analyzed retrospectively.Results:All the three patients were middle aged and old men with a chronic progressive course, beginning with weakness of one or both lower limbs, followed by dizziness, dysarthria, dysphagia, sphincteral disturbances, constipation and orthostatic hypotension. Three patients all experienced misdiagnosis (hydrarthrosis, cerebral vascular disease, alcoholism, respectively) at early stage of the disease. Cranial magnetic resonance imaging (MRI) showed mild supratentorial periventricular leukodystrophy, which was not specific. Sagittal cranial MRI demonstrated medulla oblongata and upper cervical cord atrophy called “tadpole atrophy”, which had high suggestive value. The results of gene analysis showed heterozygous mutation of glial fibrillary acidic protein gene, which had been reported as pathogenic gene; c.1091C>T (p.A364V) in exon 6, c.722C>T (p.R258C) in exon 4 and c.197G>A (p.R66Q) in exon 1, respectively.Conclusions:Type Ⅱ Alexander disease is an autosomal dominant disease, most with point mutations, rarely with deletion mutations. Type Ⅱ Alexander disease should be suspected when a patient had signs of lower brainstem involvement such as dizziness, ataxia, pyramidal sign, autonomic dysfunction, especially when cranial MRI showed mild supratentorial leukodystrophy, and medulla oblongata and upper cervical cord atrophy.

Platinum-based anticancer drugs have been becoming one of the most effective drugs for clinical treatment of malignant tumors for its unique mechanism of action and broad range of anticancer spectrum. But, there are still several problems such as side effects, drug resistance/cross resistance and no-specific targeting, becoming obstacles to restrict its expanding of clinical application. In recent years, supramolecular chemistry drug delivery systems have been gradually concerned for their favorable safety and low toxicity. Supramolecular macrocycles-platinum complexes increased the water solubility, stability and safety of traditional platinum drugs, and have become hot focus of developing novel platinum-based anticancer drugs because of its potential targeting of tumor tissues/organs. This article concentrates in the research progress of the new drug delivery system between platinum-based anticancer drugs with three generations of macrocycles: crown ether, cyclodextrin, cucurbituril and calixarene.

Inborn errors of metabolism (IEMs) are defined as genetically enzymatic deficiencies or defects in polypeptide or protein involved in cellular metabolism,which include nearly a thousand kinds of genetic-definite disease entities up to now and could develop symptoms and signs at any age,and those whose onset-age is more than 1 years old are named as late-onset IEMs.More than 80％ of IEMs could involve the nervous system,also called IEMs of the nervous system,and most of the late-onset IEM patients will go to the Deparment of Neurology firstly.The treatment aim of IEMs is to correct the metabolic deficiency.The main therapeutic strategies include substrate-limitted intake,enzyme replacement therapy,clearance of the toxic metabolites,cofactor supplement,gene therapy and sympatomatic and support treatment.Many kinds of late-onset IEMs of the nervous system are treatable,and could be healthy living if treated early and correctly.Therefore,it is important to strengthen the understanding of neurologists on the late IEMs of the nervous system,which should not be ignored.