The National Institute on Aging-Alzheimer's Association (NIA-AA) research framework of biological definition of Alzheimer's disease 2018 is introduced to Chinese counterparts to share a common "language" with dementia researchers.The abnormal definitions of Alzheimer's disease (AD),βamyloid deposition (Aβ) and tau,were proposed to be detected by biological methods,and a series of changes before dementia and dementia were proposed to be studied under a unified biological framework.The characteristic biomarkers were defined as AT(N):A is [β amyloid deposition,T is pathological tau protein,and (N) is neurodegeneration.The diversity of the pathological nature of dementia was emphasized,and AD combined with dementia was proposed not to be directly attributable to dementia due to AD.The definition of biomarkers requires more standardization and confirmation of autopsy pathology.

Objective To analyze the clinical and histology characteristics of a patient with frontal lobe epilepsy diagnosed with mild malformation of cortical development with oligodendroglial hyperplasia, and to recognize the new neuropathological entity. Methods Clinical history, seizure types, neuroimaging, electroencephalography as well as macroscope, histology and immunohistochemistry characteristics were collected from a frontal lobe epilepsy patient and were compared with cases from literature. Results It was a female patient aged 16 years with 12 years history of epilepsy. The seizures manifested as episodes of conscious loss with automatism including grope and voice lasting for seconds. About 10 episodes a day were found and sometimes with secondary generalized tonic-clonic seizures. MRI showed blurring of grey-white matter interface in left orbital frontal cortex. Video-encephalography revealed left frontal lobe origin of seizures. So left prefrontal lobe was removed. Histology showed almost normal cortex neuropil and neurons. Blurring of grey-white interface in some area with patches of proliferation of oligodendrocytes in the corresponding sub-cortical white matter was found. The density of oligodendrocytes was significantly higher in sub-cortical than in deep white matter both shown in HE and Oligo-2 staining. Obvious oligodendrocytes increase and satellite phenomenon in deep cortical layer as well as increased ectopic neurons in sub-cortical white matter were found in the lesion. In proliferation area, there were some nuclei stained with Ki-67, but not as high as tumor. Subsequent follow up for two years proved the operation efficacy and benign prognosis. Conclusions There are special and undiscovered histopathological entities in epilepsy etiology. Although known as grey matter disease, white matter pathology plays an important role in epilepsy pathophysiology which needs further research.

Objective To observe the pathological changes of pituitary tissue in rats with acute necrotizing pancreatitis and to explore the mechanism of pituitary tissue injury in rats.Methods 24 SD rats were randomly divided into normal group (N group,n=8),sham operation group (SO group,n=8),and acute necrotizing pancreatitis group (ANP group,n=8).ANP model was established by retrograde injection of 5％ sodium taurocholate into the biliopancretic duct.The serum levels of amylase(AMY) and lipase (LIP) were detected by automatic biochemical.The serum levels of growth hormone (GH),adrenocorticotropic hormone (ACTH),thyroid stimulating hormone (TSH) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay.The pathological changes of pancreatic tissue and pituitary tissue were observed by the light microscope.The expression of Casepase3,Caspasel2 and CHOP in pituitary tissue were determined by immunohistochemical method.Results Compared to SO group,the serum levels of AMY(8679.16±307.60) U/L and LIP(9376.83±380.92) U/L were significantly higher in ANP group (P＜0.05).The serum levels of ACTH (0.92±0.41) pg/ml,TSH (0.14±0.06) pg/ml,and FSH (2.01±0.38) pg/ml were significantly lower in ANP group(P＜0.05).The expression of Caspse 3 (65.66±7.58),Caspase12(70.66±4.76) and CHOP(143.16±19.05) in pituitary tissue were significantly increased in ANP group (P＜0.05).The pancreatic injury was more severe in ANP group under light microscope (P＜0.05).The degree of hyperemia of pituitary tissue of ANP group was aggravated.Conclusion Pathological changes occur in rat pituitary tissues and endoplasmic reticulum stress injury plays a role in pituitary injury during ANP.

Objective To explore the effects of electroacupuncture on brain derived neurotrophic factor (BDNF) of rats with sciatic nerve injury (SNI); To discuss its biological mechanism for treatment of SNI. Methods Fifty adult male Wistar rats were chosen, and the sciatic nerves of rats were cut off and pulled on both sides of the cut ends into nerve regeneration chamber. The rats were randomly divided into normal group, sham-operation group, model group, and electroacupuncture group. In the electroacupuncture group, the rats were treated by electroacupuncture for 28 days. After the treatment, the nerve regeneration was observed through HE staining. Immunofluorescence was used to analyze the expression changes of BDNF in the nerve tissue and spinal cord. ELISA was used to observe the changes of expression of serum BDNF. Results The amount of axon regeneration in the electroacupuncture group was obviously more than that in the model group, and the outline of the tissue more clear. Electroacupuncture could promote the expression of BDNF in the nerve, spinal cord and serum of SNI of rats compared with model group (P<0.01). Conclusion Electroacupuncture can promote the repairment and regeneration of SNI in rats by upregulating the expression of BDNF.

ObjectiveTo investigate the clinical and pathological characteristics of dermatomyositis with muscular perifascicular atrophy (PFA).MethodsA series of 104 consecutive patients clinically and pathologically diagnosed as dermatomyositis by muscle biopsy in our laboratory from December,2003 to August,2011,were enrolled in this study. Muscle biopsy of all the enrolled patients had shown PFA of muscle fibers.ResultsAmong the 104 patients,34 were males and 70 were females with a mean age of 45 years old.Among them,8 cases had normal electromyogram;42 had normal serum creatine kinase level;11 were diagnosed as carcinoma;75 were found to be combined with interstitial lung disease (ILD).Based on morphologic changes of muscle biopsy,they were divided into pure PFA group with 54 cases and PFA plus focal damage group with 50 cases.Compared with the pure PFA group,there was prominent mononuclear cell infiltration into perimysial intermediate sized vessels and membrane attack complement (MAC) deposition in the intramuscular capillaries in the PFA plus group.Skin biopsy had been taken in 12 cases together with muscle biopsy and had shown the border effectof both PFA and interface dermatitis in muscle and skin.ConclusionsOur study suggests that chronic immune vascular damage and insufficiency in dermatomyositis may cause ischemia and focal myofiber damage in watershed regions. The incidence of ILD in our dermatomyositis patients with PFA is high.

ObjectiveIn an attempt to clarify the usefulness of combined nerve and muscle biopsy in the diagnosis of neuromuscular disease when compared with traditional sural nerve biopsy.Methods Fifteen biopsies of superficial peroneal nerve (SPN) and peroneus brevis muscle ( PBM ) by one incision performed within one neurological clinic were reviewed.All patients had peripheral neuropathy while 3 of them had myopathy clinically.The diagnostic significance of SPN and PBM biopsies were classified into 3 grade: essential,helpful,no value.ResultsOf 15 SPN and PBM biopsies,7 showed essential pathological findings whichreachedthe etiologicaldiagnosis, including 5definitevasculitis, 1inflammatory demyelinating polyneuropathy and 1 amyloid neuropathy.Five biopsies are helpful for etiological diagnosis,including demyelinating neuropathy,mild inflammation,and microvascular lesion,et al.Three biopsies are of no value for etiological diagnosis which only have nonspecific change such as type 2 fiber atrophy,neurogenic atrophy and axonal degeneration et al. Finally,SPN and PBM biopsies made the definite etiological diagnosis possible in 12 patients.ConclusionsSPN and PBM biopsy improved the yield of specific pathological and etiological diagnosis of neuropathy and myopathy such as vasculitis and amyloidosis with minor trauma and side effect.Further clinical and pathological studies will be necessary for a better practice of combined nerve and muscle biopsy.

Objective Standard neuropsychological assessment plus structural and functional imaging were used in accurate diagnosis of Benson's syndrome (posterior cortical atrophy).Method Serial neuropsychological screening and integrative assessments of visual spatial function, 3D structural MRIimaging and functional FDG-PET imaging were used in two cases of Benson' s syndrome.Results The clinical signs were agnosia, optic ataxia, apraxia, alexia, agraphia and prosopagnosia.MRI imaging revealed bilateral parietal and occipital lobe atrophy.FDG-PET imaging revealed low metabolism in the posterior cortex.The agraphia was constructive: the words were correct but written in the wrong location.Conclusion Standard neuropsychological assessments can recognize the disease nature.When combined with the structural and functional imaging, a correct diagnosis of Benson's syndrome can be made.

Objective To summarize the clinical and pathological features of glycogen storage disease (GSD) type Ⅱ. Methods The clinical and pathological data of the 20 GSD type Ⅱ patients were reviewed. Results One patient with infantile-onset mainly presented hypotonia, muscle weakness, feeding difficulties, pulmonary infection and cardiomyopathy insufficiency and increase of serum creatine kinase (778 IU/L) and echographic evidence of hypertrophic cardiomyopathy were detected. Electromyography studies indicated a definite myopathy. Nineteen cases were late-onset, presenting a slowly progressive proximal myopathy with truncal involvement or with symptoms dominated by respiratory insufficiency. Not all muscles were equally affected. Increase of serum creatine kinase (208-2600 IU/L) was detected in 14 patients and normal level in 1 patient. Electromyography studies indicated a definite myopathy in 9 patients,with abnormal irritability in 1 patient and susceptible in 4 patients and myotonic discharge in 1 patient and no abnormalities in 2 patients. Echographic evidence of thickening of the interventricular septum and pulmonary hypertension were detected in 2 patients respectively. The common light microscopic feature of all case was a vacuolar myopathy with high glycogen content and acid phosphatase activity in the vacuoles. Conclusions GSD type Ⅱ often presents slowly progressive myopathy which often affect the toro and respiratory muscles.In most patients the serum creatine kinase level is elevated slightly. Muscle biopsy is of use to make the definite diagnosis of this disease.

Objective The clinical,laboratory,and neuroradiologic features of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) were analyzed and early clinical diagnosis was proposed.Method The various presentations of 34 MELAS patients were summarized to identify the specific symptoms and signs.The appropriate interpretation of the ancillary examinations,including lactic acid levels of blood and cerebral spinal fluid,neuroradiology,muscle biopsy and genetic test,was emphasized.the diagnostic significance and limitations of clinical,laboratory and neuroradiologic features were pointed out.Result The most common clinical presentations were listed in order of frequency:seizures,headache,mental decline,stroke-like episode,development abnormality,muscle weakness,fatigue,and ophthalmoplegia.Raised fasting or post-exercise blood lactic acid levels were found in 23 patients (67.6%).The most common lesions were located in the occipital lobe,parietal lobe,temporal lobe,basal ganglion,frontal lobe,cerebellum and deep white matter of 32 patients.Ragged red fibers were found in 24 patients (75%),and 8 other patients had negative muscle biopsy.Fourteen patients underwent genetic test,of which 9 patients had point mutation at 3243.Conclusion It is feasible to have early recognition of the various presentations of MELAS and make an early diagnosis even before the stroke like episodes.

Objective To investigate the value of the immunohistochemistry and Western blot in the diagnosis of the benign muscular dystrophy with abnormal dystrophin expression.Methods The medical histories and clinical manifestations of 4 patients were collected.In addition to routine histological and histochemical studies,expression of dystrophin in muscle fibets was observed by immunohistochemical reaction(dys-N,dys-R and dys-C)and Western blot to anti-dystrophin antibody.Results Two patients had muscular weakness while another 2 patients had only muscular pain and elevated creatine kinase blood levels without muscular weakness.Histochemical stains showed atrophy,hypertrophy and fiber splitting in 2 patients,while only variation in fiber size was presented in anothor 2 patients.One patient had no reaction for dys-N,but had immunostains for dys-C and dys-R in the sarcolemma of muscle fibers.Western blot confirmed that the band of dys-C and dys-R was partly deficient,and the band of dys-N was absent compared with control.Three patients had no reaction for dys-R,but had immunostains for dys-C and dys-N.Compared with control,Western blot confirmed that the band of dys-R was absent,and the band of dys-C and dys-N were truncated.Conclusion The immunohistochemistry is stained with three anti-dystrophin antibodies to avoid diagnostic errors.Western blot is essential to further determine the type of dystrophin protein.