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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Objective To analyse the neuropsychological changing of nonfluent aphasia frontotemporal dementia (nf-FTD) with the FDG-PET, MRI and fMRI. Methods The language and other cognitive function were dynamically estimated by standard neuropsychological assessment which modified by Chinese. Compared with FDG-PET and fMRI, the relationship between the neuropsychologieal changing and the cortex function was studied. Results All the 5 patients met the criteria of nf-FTD by Association for Frontotemporal Dementias, with core syndrome and other supptted syndrome. And still they had the good word reading, calculation by pen, and the un-speechmemory. And they also had the related well living ability. They all had the related cortext metabolism support. Conclusions nf-FTD patients preserve the word reading, visuapacial ability and calculation by pen. These can help us to give the effective advise about the patients training and caring and to give them the chance to show their real social skill.
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Objective To find out a reference range of epidermal nerve fiber density in normal humans and compare the concordance between clinical features, electrophysiology and the results of skin biopsy. Methods Fifty-one patients with peripheral neuropathy and 10 normal controls were studied. Skin biopsies were obtained from distal leg and/or proximal leg and nerves identified using immunohistochemistry with antibody against protein gene product (PGP) 9. 5. Forty-one in 51 performed routine nerve conduction vdocity and electromyography, 21 in 51 performed sympathetic skin response(SSR). The concordance of the consequences was compared. Results Intraepidermal nerve fiber density (IENFD) was (21.4 + 2. 7) /mm in thigh and (15.4±2. 2) /mm in the distal part of the leg in normal controls. IENFD was (15.0± 6. 3)/mm and (8. 1±5.9) /mm in patients. The intraepidermal nerve fiber density was significantly lower in the patients than in the normal controls both in proximal (t = 2. 976, P = 0.004) and distal legs (t= 3.191, P=0.002). Forty-eight out of 51 patients showed abnormalities in skin biopsy, among which 33 patients had length-dependent neuropathy. In the group of abnormal skin biopsy, 41 received routine electrophysiology, among which 21 (51.2%) were abnormal and they were performed SSR, turning out that 17 (81.0%) were abnormal. In 29 patients who had only small fiber neuropathy, 27(93. 1%) showed abnormalities in skin biopsy, out of whom 20 were performed routine electromyography, and it identified that 6 (30. 0%) were abnormaL In 14 receiving SSR, 11 were abnormal. Conclusion Skin biopsy is safe and tolerable, which has a higher sensitivity especially in small fiber neuropathy.
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Objective Some cases of lipid storage myopathy (LSM) are similar to the polymyositis(PM) in clinic.To study the muscle pathology is helpful as to making clear the diagnosis and elucidating the mechanism of the LSM. Methods 14 cases of LSM with high level of CK in serum were analyzed clinically and compared with their muscle morphological and histochemical changes.Results Muscle weakness and fatigue were the main complaints of these patients.Most of them had acute or sub acute onset,some of them had relapse courses.All of the muscle specimens showed typical accumulation of lipid in muscle fibers.Necrotic fibers were found in 9 cases,3 of them showed changes with the courses. Conclusion Muscle biopsies and histochemical studies are necessary to differentiate LMS with PM.The fiber necrosis and CK leakage in LSM may be caused by changes of the inter circumstance and the membrane disturbance of cells.
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Objective To prove whether it is availble to define the penumbra histopathologically and immunohistopathologically by observing the MRI T 2 imaging,cytoskeleton and neuron changing. Methods Seven cases of autopsy infarct brain with different ischemic time were studied in our program. By MRI T 2 imaging, the fixed brains were examined. Large section of whole brain, and small section of different parts,in and out of the infarct area, and the opposite hemisphere were observed. After observing the neuron, cytoskeleton, microglia, astrocyte, vessel, and also some cytokines by histological and immunohistochemical methods, we divide the ischemic and surrounding areas into four different parts as to seeing the different changes. Results In area 0, the neuron, gliocyte and vessel were all necrotic, eosinocytes developed, and cytoskeletons disappeared. In area 1, there were large number of dark neurons, shrinking cells with heavily destroyed, cytoskeleton, active microglia and inflammatory cells. In area 2, there were a few ischemic neurons , a few dark neurons, and normal neurons,and were also lots of active astrocyte and microglial. The proportion of area 2 was reduced sharply in two days. The ischemic proportion shown by MRI was smaller than that shown by large section of the whole brain. MRI T 2 imaging showed only the area 0 and area 1 with T 2 value increasing, and not showed the area 2 with normal T 2 value. In area 3, the cells were all in normal shape.However,the active microglia and astrocyte hyperplasia, together with the positive TGF ? and TNF? expression, existed in area 3 in all seven brains.Conclusions Area 0 is the infracted mature area, area 1 is the irreversible area, both of them are centers of the necrotic area. Combined with MRI, neuron and cytoskeleton changes, we conclude that area 2 is the possible reversible damage area, or the equal area of penumbra. Area 3 is the response area to ischemic damage, which in some authors’studies was called‘penumbra’.
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Objective To analyze the clinic and pathological features of Castleman’s disease (CD),or an angiofollicular lymph node hyperplasia(ALNH) Method Retrospectively gave a review of 6 patients with CD in recent 15 years in PUMC Hospital Results 4 patients with multicentric Castleman’s disease (MCD) had systemic symptom including fever,anemia,edema and endocrine disorders M protein presented in 3 of them 3 patients with MCD had progressive polyneuropathy,with presenting distal symmetric weakness and numbness, areflexia Nerve conduction velocity was slow and action amplitude decreased significantly.Sural nerve biopsy showed a moderate? prominent axon degeneration with minimal vasculopathy 2 patients with localized CD (LCD) had no systemic or neurological complications Histological study of lymph tissue confirmed the diagnosis of CD,showing that there were subtype of hyaline vascular (HV) in 5 cases and plasma cell (PC) in 1 case Conclusion Multicentric Castleman’s disease should be associated with systemic and neurological involvement It might present with distal symmetric motor sensory axonal polyneuropathy The clinic feature should be a PEOMS syndrome with a poor prognosis
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Objective To investigate the clinical manifestions ,neuropathology and imaging in the patients with MELAS type of mitochondrial encephalomyopathy for exploring the diagnostic method of the disease. Methods Systemic study was performed on the clinical features,imaging of four MELAS patients. Muscle biopsy and 2 brain biopsies of 3 cases were examined. Results The main clinical features were characterized by intolerance to exercise,recurrent headache and vomit,focal or generalized seizures,dementia,stroke like episodes,sensorineural deafness, hypertrophic cardiomyopathy,endocrine dysfunction,short stature,lactic acidosis and so on. Electromyography showed myopathic damage. CT showed calcification in basal ganglia. CT showed multiple low density lesion primarily in gray matter of occipital,parietal and temporal cortex,which was expressed by the abnormal longer T 1 and T 2 weighted signals on MRI.Muscle biopsy showed red ragged fiber and abnormal mitochondria. Brain biopsy showed laminar necrosis of cortex,astrocytosis,diffused microvascular proliferation and calcification. Four cases were diagnosed as MELAS type.Conclusion According to clinical manifestations and neuroimage features,MELAS is possibly early defined in combination with muscle or/and brain biopsy.
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Objective To study the frequency and correlate factors of lipid accumulation in muscle fibers in inflammatory myopathies Methods Muscle biopsy specimens were routinely processed for histopathological and histochemical studies Excepting inflammatory changes, lipid droplets were observed by ORO staining According to the amount of lipid droplets in the muscle fibers, these cases were separated into two groups, and then the differences in muscle power, serum CK level, morphologic changes of muscle, courses and corticosteroids administration between two groups were compared Results 37 7% specimens showed lipid accumulation in muscle fibers distinctly As compare with the lipid normal group, in the lipid increasing group, the generalized muscle fiber degenerating were more common and muscle weakness were more prominent Although more patients have long term therapy with steroid in lipid increasing group, there were no significant differences between these two groups Conclusions Lipid accumulation in muscle fibers was present in some patients with inflammatory myopathies Increasing of lipid droplets might result from the muscle fiber degenerating and might turn to impair the muscle function reversely