Creutzfeldt-Jakob disease (CJD) was first described as a clinical entity in the 1920s in Germany by Hans Gerhard Creutzfeldt and Alfons Jakob as a subacute spongiform encephalopathy and represents the prototype of a set of rare degenerative neurological conditions , which affect the human being. They are called transmissible spongiform encephalopathies (TSEs) due to experimental studies that demonstrated their transmissibility to animals and due to their neuropathological characteristics such as spongiform changes (Vranjac, 2008).
Most cases of sporadic creutzfeudt jacob have characteristic clinical findings including rapid progressive dementia, myoclonus, and periodic sharp-wave electroencephalography (EEG) complexes (Iwasaki et al., 2017).
Creutzfeldt-Jakob disease (CJD) is the most frequent human prion disease - a group of rare diseases referred to as spongiform encephalopathies. It is a rapidly progressive dementia, with pyramidal, extra-pyramidal, cerebellar and typical electroencephalogram changes. It presents an incidence of 0.4-2.5 / 1
million inhabitants / year, average age of 60 years and similar distribution between men and women (Neitzke et al., 2009).
Creutzfeldt-Jakob disease (CJD) is classified as familial (f), sporadic (s) or iatrogenic (I) or variant (v). Typically, it presents weeks to months before the observation of progressive mental deterioration (85%) or cerebellar signs (56%). Familial CJD is an autosomal dominant inheritance, condition resulting from a mutation in the prion protein gene on chromosome 20. Familial CJD differs from sporadic CJD, both in terms of age of onset (fifth vs. sixth decade of life) and duration of the disease (longer in the CJD family). In contrast, CJD variant is an acquired form of the disease; this is presumed due to the consumption of bovine spongiform encephalopathy (BSE) cattle (Brett et al., 2017).
The normal cellular prion protein, identified by the abbreviations PrP or PrPc, is a normal cellular protein present in several cell types, including muscle and lymphocytes. The prion infectious protein can be abbreviated by PrPsc, and this infecting agent is tropism by the neural tissue. The normal, non-pathogenic cell form (PrPc) has a predominantly alpha helical conformation, whereas the infecting form, PrPsc (originating from the scrapie denomination) has a beta-sheet structure (as a pleat sequence). Accumulated prions join together to form fibrils or plaques, which have toxic effects on cells, particularly neurons, thus forming large vacuoles on amyloid plaques (Vranjac, 2008).
This study was a systematic review of the neurological changes due to creutzfeldt-jacob disease. The following keywords were used: "Creutzfeldt-Jacob Syndrome", "Neurologic Manifestations", "/ diagnosis" and "Pathological Conditions" , Signs and Symptoms. We included studies addressing creutzfeldt-jacob alterations, mainly in the neurological system, written in English and that have been published in the last 10 years. We excluded studies that did not address the topic in question, which did not bring clear information that was not in the English language and that exceeded the delimitation of the research time.
Four articles were found, all of which were case studies of patients with creutzfeldt-jacob disease, and the symptoms presented by the study were analyzed gradually over months. The first symptom presented in 2 of the articles were headache, apathy, progressive disorientation memory disorders, personality disorder, hallucinations and speech disorder (Iwasaki, 2017) (Tiriba, 2011). Already in the other 2 case reports present gait changes, such as myoclonus first and later ataxia and signs of hypertonia and hyperreflexia (Neitzke et al, 2009) (Hettige, 2017). But all 4 articles in the course presented both symptoms, changing only the order of appearance of each one of them. About one-third of the patients start with focal signs, ataxia, aphasia, visual loss, hemiparesis, amyotrophy, myoclonus, rigid posture. It evolves with akinetic mutism and death in 100% of cases. The diagnosis is suspected by rapidly progressive dementia in all cases (Neitzke et al., 2009). There is no laboratory marker for creutzfeudt. The electroencephalogram (EEG) is altered in the vast majority of patients, regardless of the variety and stage of the disease. Classically, it presents periodic complexes of high voltage in intervals of 0.5-2 seconds (three-phase waves). Precociously, it presents a slow, diffuse or lateralized base rhythm, with epileptiform discharges (responsible for myoclonus). It is a non-invasive examination of great diagnostic importance, with specificity of 86% and sensitivity of 67%. These changes, however, may occur in Alzheimer's disease, brain abscess, metabolic encephalopathy, progressive multifocal leukoencephalopathy and lithium and bismuth intoxication (Neitzke et al., 2009). According to the case study of Iwasaki et al. (2009), in order to close the neurological diagnosis of the disease, it is necessary to perform initial laboratory tests that show no change in the result. Computed tomography (CT) and nuclear magnetic resonance (MRI) of the brain were also presented as normal. CSF examination was
normal. During the investigation, the patient evolved with generalization of the condition, myoclonus and accentuation of episodes of dystonia. Performed on electroencephalogram (EEG), which showed repeated high voltage three-phase discharges. The exams were performed monthly to assess significant neurological changes. The patient progressed rapidly with myoclonus worsening, lowering of consciousness level and episodes of focal seizures. In the performance of the new CT scan of the skull was normal the CSF maintained the same pattern. Due to the suggestive clinical picture and the typical EEG, prion disease was hypothesized. The 14-3-3 protein in the cerebrospinal fluid was positive at an advanced stage of the disease. Despite clinical support, there was a progressive worsening of the condition with death to five months after the onset of symptoms. Necroscopic findings confirmed the hypothesis of prion disease. In the four studies of 4 the alterations were also not significant to compare with the symptoms presented by the patient, I then feel only confirmed in the cerebrospinal fluid at an advanced stage of the disease, becoming then a fatal disease in all its cases.
Studies show that creutzfeldt-jakob disease are still difficult to prove the symptoms with the patient's neurological condition, since the responses presented by the patient do not agree with the onset of neurological examinations, delaying to present significance in the imaging examinations, the diagnosis becomes more difficult, making the disease necessary for further studies to improve the diagnostic and treatment method for patients with the disease, so that better patient survival is achieved.



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Creutzfeldt-Jakob disease with a prion protein gene codon 180 mutation presenting with pathological laughing and an exaggerated startle reaction Japanese Society of Neuropathology, 2017.


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