Creutzfeldt-Jakob disease dementia
Introduction
Introduction to gram-Alex's disease dementia Creutzfeldt-Jakob disease is a prion (protein) disease and is a central nervous system degenerative disease caused by prion protein transmission. The disease has a long incubation period and a short course of disease, and it usually dies within 1 to 2 years. Dementia is continuously progressive. By the 1950s, Sigurdsson (1954) studied laryngeal encephalopathy with laryngeal encephalopathy. The prion protein gene (PRNP) is located on the short arm of chromosome 20, and prion protein exists in two forms in vivo, one is normal cell. The isomer (PrPc) is synthesized by the endoplasmic reticulum and has a short half-life of 3 to 6 hours. The structure of this protein is mainly composed of -helices, and -sheets are rare. No pathogenic effect, another pathogenic pruritic isomer (PrPsc), protein structure helix is very small, mainly composed of -fold, the translation process is slow and not easy to degrade and cause disease in cell membrane, especially synaptic membrane deposition. . basic knowledge The proportion of illness: 0.005% Susceptible people: good for people aged 40 to 65 Mode of transmission: iatrogenic transmission Complications: pneumonia
Cause
Cause of gram-Yan's disease dementia
(1) Causes of the disease
The disease is caused by a prion infection in a lentivirus, and is a disease caused by the transmission of prion protein. It is a central nervous system called a scrapie-specific protein granule with a diameter of 10-20 nm and a length of 100 nm. Systemic degeneration, cerebral cortical neuronal degeneration, astrocytic hyperplasia and spongiform changes, etc., the path of transmission of this disease is not very clear, about 10% of patients with family transmission, and a few for iatrogenic transmission, such as corneal transplantation Or onset of treatment with biological products.
(two) pathogenesis
Because the scrapie-specific protein is an unconventional factor, it is not immunogenic. After entering the body, it can not stimulate the body to carry out the humoral immune response of the cells. Therefore, once infected, the pathogen cannot be removed, and the cerebral cortex has pathological spongy changes and nerve cells are reduced. , degeneration and astrocytic hyperplasia, etc., classic early only generally mild brain atrophy, microscopically showed cerebral cortex gray matter can vary in size, round and oval vacuoles are spongy changes, neuronal degeneration is reduced and off Loss of astrocyte hyperplasia, no inflammatory cell infiltration, positive immunohistochemical staining for PrP, occasional amyloid plaques in Congo red staining, membranous vacuolar degeneration and pruritus-related fibers (SAF) seen by electron microscopy.
In the advanced stage, the cerebral cistern is widened, the brain is flat and severe brain atrophy, and there is no inflammatory exudation and focal brain lesions. Pathological spongiform changes are mainly found in the cerebral cortex, and the distribution is mainly , frontal and occipital. The parietal lobe and central gyrus are the lightest, the basal ganglia caudate nucleus, caudate nucleus and thalamic lesions are obvious, while the globus pallidus is lighter, the cerebellum, midbrain, pons and medulla also have spongy changes, and nerve cells reduce degeneration and Astrocyte hyperplasia, the anterior horn of the spinal cord can be affected but lighter, and the spongiform changes are severe in the short course of the disease. The neuronal degeneration and astrocytic hyperplasia are obvious in the long course.
The new variants are similar to the classic spongy changes, neuronal degeneration and astrocytic cell proliferation, and positive for PrP, but the degree and distribution of lesions are different. For example, the thalamic and cerebellar lesions are obvious, and the Congo red staining amyloidosis is more than the classic one. see.
Prevention
Gram-Arabid Dementia Prevention
The experiment proves that the patient's brain tissue vaccination has a high incidence rate and a long incubation period, but its infection route is unknown, and preventive measures should be taken actively.
1. Strictly monitor iatrogenic infections such as corneal transplantation, bone marrow transplantation, biological agents, and growth hormone to prevent infection.
2. Although there are no reports of infection and disease in patients, there are wounds such as blood sampling, cerebrospinal fluid, scalp puncture, and brain biopsy. Strictly implement disinfection and isolation to prevent infection.
(1) Try to use disposable instruments such as syringes and needles, and use post-treatment to strictly manage them.
(2) For instruments that cannot be used once, it can be set up for CJD brain biopsy instruments, not for general patient surgery, special disinfection measures, 132 °C autoclave for more than 60 min or 5% bleaching powder or 2 mol/L sodium hydroxide 60min.
(3) The patient's biopsy or autopsy brain tissue is strictly managed, and the treatment of its pollutants must be incinerated.
Complication
Complications of gram-arthritis dementia Complications pneumonia
Like other serious diseases, it is easy to suffer from secondary infections in various systems, especially with progressive pneumonia and urinary tract infections.
Symptom
Symptoms of gram-Aristotle's disease dementia Common symptoms Dementia limb weakness Inability Dementia Anxiety Apathy Consciousness Fuzzy Sensory Disorder Illusion Vision Deformation Depression
The disease is rare, the incidence rate is about one in a million, the male and female prevalence are equal, the age of onset is 40 to 65 years old, but it can occur in various stages of adulthood, mostly sporadic cases, the transmission route is not very clear, About 10% of patients have family transmission, and a few are iatrogenic, such as corneal transplantation or biologic treatment. The course of the disease is subacute, and the development is faster than other primary dementia. It often dies within 1 to 2 years. .
The prodromal period is several weeks or months as a symptom of neurasthenia. It can also cause attention and memory disorders, limb weakness and gait instability, and the intelligence rapidly declines. The neurological symptoms also become prominent, and there may be cerebellar ataxia. Extremities and progressive paralysis of the extremities, cone and extrapyramidal symptoms such as tremor, dance-like movements, etc.; speech disorders are common; computational disorders can also occur, can not distinguish between left and right parietal symptoms, visual acuity can be severely affected, rapid progressive cortical Blind, such as brain stem damage can have nystagmus, difficulty swallowing or mandatory crying, often muscle shock, seizures, and some may have acute brain organic syndrome, such as confusion, ambiguous, There may be hallucinations, delusions, and finally paralytic palsy and severe dementia.
There are two types: classic and new variants, which are explained as follows:
1. Classical clinical manifestations in the elderly, age 50 ~ 70 (65) years old, with subacute onset, early patients with prodromal symptoms similar to cold fatigue, fatigue, lack of attention, mental distraction, irritability, irritability Other mental behavior abnormalities; some patients have dizziness, dizziness, limb weakness, walking instability, visual symptoms: vision loss, diplopia, visual distortion, and even visual hallucinations, rapid progression of involuntary movements, slow movements, muscle rigidity, Tremors, hand and foot movements and dance symptoms, most patients have myoclonus twitching, repeated attacks, and can be induced by acousto-optic stimulation, a small number of patients may have loss of mind, epileptic seizures, and soon cognitive impairment, memory loss, dementia , disorientation, mental symptoms and even paranoia, fiction, no recognition, a few excitement, dementia continued to progressively worsen, and finally bed restless.
Neurological examination signs: diplopia, nystagmus, gaze palsy; rotation test and finger-nose test can not; gait sputum, ataxia, most patients have high muscle tone, rigidity, tremor, extrapyramidal sign and limb weakness The pyramidal tract sign, etc., eventually showed a state of stupor and awakening coma.
2. The clinical manifestations of new variants are mostly in the onset of adolescence, with acute or slow onset of onset, early onset of psychiatric symptoms: apathy, low mood, depression, anxiety or anxiety, generalized malaise, and onset of weeks or months Sexual ataxia, cognitive disorders appear later, may have myoclonus twitching, dance-like movements, late memory loss, progressive dementia.
Neurological examination signs: gait instability, gait sputum, Angbo sign, cerebellar ataxia, a few patients can see facial or somatosensory disturbances, visible pyramidal tract signs and extrapyramidal signs, dementia, silence, and finally More than two years later, he died of death.
The onset is subacute, rapid progress, continuous progressive dementia, cone and extrapyramidal signs, accompanied by myoclonic convulsions, short course of disease, and more than 1 to 2 years of death, the clinical manifestations of this disease is complex, so the clinical diagnosis Difficulties, must be combined with laboratory examination and pathological examination to make a more accurate diagnosis, auxiliary examination shows that cerebrospinal fluid test is more normal, total protein occasionally increased, but immunoglobulin does not increase, gas angiography is normal or the ventricle is enlarged, There are signs of atrophy of the brain and cerebellar cortex. EEG often has obvious abnormalities. Diffuse or focal slow waves can begin to appear. Later, sharp or slow peak waves can be seen. Finally, characteristic three-phase appears on the background of cortical inhibition activity. Synchronous composite sharp waves are of great value for clinical diagnosis. Cortical atrophy and ventricular enlargement can be seen in the head CT. The pathological changes are characterized by spongiform changes, neuronal degeneration or loss and astrocytic hyperplasia, which are helpful for diagnosis.
Examine
Examination of gram-Alex's disease dementia
Cerebrospinal fluid routine, biochemical examination, except for a small number of cases with mild protein elevation (generally 50 ~ 60mg / dl), no abnormal changes, immunoglobulin (Ig) and oligoclonal bands were not abnormally expressed, recently tested 14-3- s protein positive has an auxiliary diagnostic value.
1. EEG often has obvious abnormalities. EEG examination has important auxiliary value for classical Ke-Yan's disease, and its speciality changes: in the early stage, only the wave is reduced, and the wave decreases and disappears, and the wave appears. wave, when the disease progresses, the wave disappears, and diffuse or focal slow wave appears. Later, a sharp wave or a slow peak wave, a spine-slow wave complex wave, and finally a characteristic three-phase synchronous composite appear on the cortical inhibition activity background. The sharp wave, the final EEG background electrical rest and periodic synchronous release (PSD), and the new variant Creutzfeldt-Jakob disease without this special EEG changes, can begin to appear important value for clinical diagnosis.
2. Imaging examination of head CT, no abnormal changes in early MRI, general brain atrophy in the advanced stage of the disease, wide brain pool, small cerebral gyrus and enlarged ventricles, most (80%) no focal changes, few cases of MRI found in recent years It can be seen that the bilateral base section, the T2 signal behind the thalamus, is sometimes less obvious. For example, using proton images, Flair and diffuse MRI can clearly enhance the signal, which has diagnostic significance.
3. Cerebroencephalography Normal or ventricular enlargement, there may be signs of atrophy of the brain and cerebellar cortex.
Diagnosis
Diagnosis and diagnosis of gram-Aristotle's disease dementia
Diagnostic criteria
1. Classical sporadic gram-James disease diagnostic criteria
(1) Definite CJD diagnosis:
1 has typical clinical signs and symptoms (pyramidal signs and extrapyramidal signs).
2 has continuous observation of EEG three-phase wave and periodic synchronous release (PSD).
3 brain biopsy obtained pathological support:
A. Typical spongy changes.
B. Amyloid plaque deposition, PrP immunohistochemistry ( ).
C. Electron microscopic observation: membranous vacuolar degeneration and pruritus related fibers (SAF).
(2) Probable CJD diagnosis:
1 progressive dementia.
2 typical EEG three-phase wave and PSD.
3 cerebrospinal fluid 14-3-s protein positive, clinical course <2 years.
4 with 2 of the following 4 clinical symptoms:
A. Myoclonus twitches.
B. Visual or cerebellar disorders.
C. Pyramid beam sign / extrapyramidal sign.
D. No moving silence.
(3) Susceptible CJD diagnosis: similar to Probable CJD clinical manifestations; but no typical EEG findings or atypical EEG changes; patients with a disease duration shorter than 2 years.
2. New variant CJD diagnostic criteria
(1) Clinical manifestations:
1 mental abnormalities, symptoms of depression and anxiety.
2 cerebellar ataxia occurs several weeks or months after onset.
3 memory loss, dementia in the late stage.
4 myoclonus twitching, dance-like symptoms and extrapyramidal signs.
5 limb weakness, facial and limb paresthesia, pyramidal tract sign.
6 EEG has no characteristic changes.
(2) The diagnosis must be confirmed by pathology:
1 It can be seen that the Kuru-type amyloid plaque is surrounded by vacuoles.
2 Sponge-like changes are evident in the basal ganglia.
3 The thalamus showed obvious gliosis.
4PrP deposition is found in the brain and cerebellar molecular layers.
Differential diagnosis
Characteristics of the disease: rapid onset of subacute onset, persistent progressive dementia, pyramidal tract sign and extrapyramidal sign, accompanied by myoclonic convulsions, short duration of disease within 1 to 2 years, should be associated with the central nervous system in old age Identification of degenerative dementia:
1. Alzheimer's disease is a slow-onset progressive dementia with onset of onset, CT, MRI can be seen in the frontotemporal lobe atrophy, mostly in the pre- and senile stages, with a course of 5 to 10 years, pathological changes for senile plaques and nerve fibers Tangled.
2. Picking disease begins in the early stage of the elderly, with slow progress, and has a family history. It is characterized by atrophy of the brain, personality changes, progressive dementia, CT and MRI, and the temporal lobe is obviously atrophied.
3. Huntington Chorea (Huntington Chorea) has a middle-aged onset, with a clear family history, clinical manifestations of dance signs with progressive dementia, CT, MRI showed atrophy of the caudate nucleus, lateral ventricle enlargement, the course of disease can be as long as 10 to 30 years .
4. Parkinson's disease dementia Parkinson's disease complicated by dementia is rare, only 3% to 5% of the disease, slow onset, slow movement, muscle rigidity, static tremor triad first, dementia appears, and dementia It often occurs in the late stage of the disease, and the course of disease lasts for 4 to 10 years.
