Overview of Gerstmann syndrome
Gerstmann syndrome (GSS) was first discovered and described by Gerstmann, Straussler, and Scheinker in 1936, and is named after them. It is characterized by chronic progressive cerebellar ataxia with dementia, dysarthria, and intracerebral amyloid deposits, and is mostly familial. 1981, Masters inoculated animals to confirm the contagious nature of the disease, with an average duration of 5 years. The age of onset is 43-48 years, and it is a middle-aged progressive degenerative dementia of the cerebellar spinal cord, in contrast to Creutzfeldt-Jakob disease, where myoclonus is less common.
Etiology.
GSS syndrome is a rare disease with an annual incidence of 1 to 10 per 100 million population. It has been reported to be familial, with 24 unrelated families diagnosed worldwide to date, and is caused by inherited mutations in the human prion protein gene, PRNP. Point mutations in the PRNP gene are P102L, A117V , F198S and Q217R. The pathogenesis of prions is still not very clear, and it is currently believed that prions can enter from outside the body or arise spontaneously due to genetic mutations. For infectious prions, prions can enter the human body through oral, injection, or surgical routes, and the possible pathways for prions to invade the brain tissue after entry into the human body include direct neurotransmission from the site of infection, replication in the mononuclear phagocyte system, and then diffusion through the neuronal cord, as well as hematogenous diffusion and other different routes. As well as blood-borne diffusion and other pathways, prion pathogenesis is the beginning of PrPc into PrPsc, so that PrPsc in the central nervous system in large quantities of aggregation, PrPsc how to lead to neuronal cell damage to be elucidated, the relevant research suggests that: PrPsc has neurocytotoxicity, can cause neuronal cell apoptosis; PrPc is soluble, after the conversion to insoluble PrPsc, PrPsc will be deposited in the brain tissue to form a starch. After PrPc is soluble and transformed into insoluble PrPsc, amyloid plaques are formed in the brain tissue, which leads to damage; the complex formed by combining PrPc and copper atoms has the activity similar to that of superoxide dismutase (SOD), and when PrPc is transformed into PrPsc, it leads to lack of PrPc, which reduces the activity of SOD in neuronal cells, and thus increases the sensitivity to oxidative damages caused by superoxide, etc., and increases the sensitivity of neuronal cells to high-glutamate and high-copper toxicity, which ultimately leads to the damage of neuronal cells. Increased sensitivity to high glutamate and high copper toxicity, ultimately leading to nerve cell degeneration and death.
Symptoms
1. Early stage
The patient complains of numbness, pain, abnormal sensation and unsteady gait in the calves, and the examination shows cerebellar ataxia, accompanied by muscle atrophy and weakness of the lower limbs, distal hyperalgesia, decreased tendon reflexes and other manifestations of peripheral neuropathy, and the condition further develops, mental retardation may appear, and dementia may appear late and mild, and there are some cases accompanied by pyramidal fasciculation or extrapyramidal fasciculation signs.
2. Late stage
Severe ataxia and dementia, blindness, deafness, pyramidal and extrapyramidal signs, and myoclonic seizures, especially calf muscle clonic seizures.
Examination
1. Histopathological examination
Spongy vacuoles, amyloid plaques with various morphologies, neuronal cell loss with glial cell hyperplasia, and rarely inflammatory reactions such as leukocyte infiltration can be seen in the brain tissue of the lesion.
2. Immunologic examination
Various immunological methods, such as immunohistochemistry, immunoblotting, enzyme-linked immunosorbent assay (ELISA), etc., have been used to detect PrPsc in tissues. Using anti-PrP27-30 antibody, PrPsc can be detected in the lesion tissues after dissolving PrPc by guanidinium isothiocyanate and heat treatment with compression therapy or proteinase K digestion, and the monoclonal antibody 15B3 only binds to PrPsc. The monoclonal antibody 15B3 can only bind PrPsc, therefore, PrPc and PrPsc can be recognized without the treatment of PrPc solubilization. A variety of tissues were taken, including brain, spinal cord, tonsils, spleen, lymph nodes, retina, conjunctiva and thymus, etc. By applying the method of immunoblotting, a more characteristic cerebral protein 14-3-3 can be detected in the cerebrospinal fluid, which is a kind of neuronal protein that can maintain other proteins in a stable conformation and can be abundantly but not present in the normal brain tissues. This protein is a neuronal protein that maintains the conformational stability of other proteins and is abundant in normal brain tissue but does not appear in the cerebrospinal fluid. When infected with prions, a large number of brain tissues are destroyed, resulting in the leakage of brain protein 14-3-3 into the cerebrospinal fluid.
3. Animal inoculation test
Inoculate the suspected tissue homogenate intracerebrally or orally in animals (commonly used rats, sheep, etc.), observe the development of the inoculated animals, and after the development of the brain tissue biopsy to see if it has the characteristic pathological changes of prions, the sensitivity of this method is limited by the interspecies barrier, and it takes a longer period of time.
4. Physical examination
Electroencephalogram (EEG) may show characteristic periodic sharp compound waves (PSWC), which is an aid to diagnosis. In addition, computed tomography (CT) and magnetic resonance imaging (MRI) brain imaging can be used to differentiate prion diseases from other central nervous system disorders.
5. Molecular biology
DNA is extracted from the patient’s peripheral blood leukocytes, and PCR amplification and sequence determination of PRNP can reveal the characteristic mutation of PRNP in familial hereditary prion diseases.
Diagnosis
The definitive diagnosis of prion disease depends on the pathologic examination of brain tissue, so prenatal diagnosis is difficult.
1. Epidemiologic data
Consumption of food from animals suspected of having BSE, transplantation of organs from potentially prion-infected donors or implantation of electrodes potentially contaminated with prions, use of human hormones from organ sources, and a family history of prion disease are helpful in the diagnosis of the disease.
2. Clinical manifestations
Although most prion diseases present with progressive dementia, ataxia and myoclonus, different prion diseases have their own characteristics. For example, sporadic Creutzfeldt-Jakob disease has an older age of onset, and most often is followed by dementia and then ataxia, while the newer variant of Creutzfeldt-Jakob disease has a younger age of onset; Crouse disease with a significant tremor is often preceded by ataxia and followed by dementia; Jetzmann-Streussler-Schmuck syndrome is often followed by cerebellar damage such as ataxia; and Jetzmann-Schmuck syndrome is often accompanied by cerebellar damage such as ataxia and other cerebellar damage. Ataxia and other cerebellar damage, dementia is rare; fatal familial insomnia is characterized by progressively aggravated persistent insomnia.
3. Laboratory examination
Spongiform pathological changes in brain tissue and PrPsc-positive immunologic tests are important in confirming the diagnosis of the disease: cerebrospinal fluid encephalin 14-3-3 and electroencephalographic PSWCs are of supplementary diagnostic value, and genetic analysis of base mutations in PRNP sequences is helpful in the diagnosis of familial prion disease.
Treatment
Symptomatic and supportive treatment can reduce symptoms and improve quality of life, but there is no effective treatment for the pathogen. It has been reported that Congo red, dimethyl sulfoxide, phenothiazine, chlorpromazine, branch polyamines, phospholipase C, anti-prion antibodies and oligopeptides may have a certain effect on slowing down the disease, but the effectiveness and applicability need to be confirmed.