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Table of Contents
CASE REPORT
Year : 2017  |  Volume : 14  |  Issue : 4  |  Page : 234-237

An intriguing case of rapidly progressive dementia: Creutzfeldt–Jakob Disease


1 DNB Internal Medicine, Institute of Neurosciences/Internal Medicine, Indraprastha Apollo Hospitals, New Delhi, India
2 Sr. Consultant Neurologist and Academic Coordinator, Institute of Neurosciences, Indraprastha Apollo Hospitals, New Delhi, India
3 Consultant Neurologist, Institute of Neurosciences, Indraprastha Apollo Hospitals, New Delhi, India
4 Consultant Physician, Institute of Neurosciences, Indraprastha Apollo Hospitals, New Delhi, India
5 Institute of Neurosciences, Indraprastha Apollo Hospitals, New Delhi, India

Date of Web Publication5-Feb-2018

Correspondence Address:
Pushpendra Nath Renjen
C-85, Anand Niketan, New Delhi - 110 021
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/am.am_44_17

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  Abstract 

Although no formal definition exists for what constitutes a rapidly progressive dementia (RPD), generally we use the term when dementia occurs in <1–2 years from illness onset, but more commonly over weeks to months. Prion diseases are the prototypical causes of RPD, but reversible causes of RPD might mimic prion disease and should always be considered in a differential diagnosis. We report the case of a 65-year-old male with progressive dementia and typical neurologic symptoms, myoclonic jerks, and magnetic resonance imaging findings of Creutzfeldt–Jakob disease (CJD). This case highlights the need for a high index of suspicion to diagnose CJD.

Keywords: Creutzfeldt–Jakob disease, dementia, electroencephalogram, myoclonus, prion


How to cite this article:
Chaudhari D, Renjen PN, Zutshi D, Ahmad K, Kumar A. An intriguing case of rapidly progressive dementia: Creutzfeldt–Jakob Disease. Apollo Med 2017;14:234-7

How to cite this URL:
Chaudhari D, Renjen PN, Zutshi D, Ahmad K, Kumar A. An intriguing case of rapidly progressive dementia: Creutzfeldt–Jakob Disease. Apollo Med [serial online] 2017 [cited 2019 Jun 27];14:234-7. Available from: http://www.apollomedicine.org/text.asp?2017/14/4/234/224737


  Introduction Top


Although no formal definition exists for what constitutes a rapidly progressive dementia (RPD), generally we use the term when dementia occurs in <1–2 years from illness onset, but more commonly over weeks to months.[1] Because these conditions are relatively uncommon, the appropriate diagnostic workup and treatments often are unfamiliar to many neurologists. Accurate, thorough, and prompt diagnosis is important as many RPDs are treatable and even curable. The subacute nature of RPD excludes other conditions with fulminant progression such as infectious or metabolic acute encephalopathies, which progress within hours or days and typically commence as an acute confusional state. In most cases, the cognitive decline observed in RPD can be attributed to a single underlying disorder. Nevertheless, a rapid course might also represent the aggravation of an undiagnosed disease attributable to a secondary cause, usually an infection or a metabolic dysregulation.[2] Various conditions involving the central nervous system can emerge as RPD including Creutzfeldt–Jakob disease (CJD) and other spongiform encephalopathies, vascular disorders, autoimmune and paraneoplastic encephalopathies, subacute infections, metabolic and toxic disorders, and systemic diseases.[2]

Prion diseases

Prion diseases are the prototypical causes of RPD, but reversible causes of RPD might mimic prion disease and should always be considered in a differential diagnosis. Prion diseases are a group of neurodegenerative diseases caused by the conversion of the normal prion protein (PrPC, prion-related protein, in which C stands for the cellular form of the protein) with a primarily helical structure into an abnormal form of the protein called the prion (PrPSc, in which Sc stands for scrapie - the prion disease of sheep and goats). Prion is proteinaceous infectious particle that has a primarily β-pleated sheet structure. Alfons Jakob described the first cases of human prion disease between 1921 and 1923 and thought his cases were similar to a young woman described by Creutzfeldt in 1920.[3],[4]

Creutzfeldt–Jakob disease

CJD is the most common human prion disease and falls into four categories: sporadic (85%), familial (10%–15%), iatrogenic (1%), and variant.[1] CJD is an illness typically involving progressive dementia with a fatal and incurable course.[5] CJD is a rare, fatal neurodegenerative disease caused by an infectious protein called prion and is characterized by spongiform changes, neuronal loss, reactive astrocytic proliferation, and accumulation of pathologic cellular protein. Clinical presentation of CJD is characterized by RPD, neurologic symptoms and visual impairment, and the development of akinetic mutism, which can mimic many neurological conditions. This case report is about a patient who presented with RPD, myoclonus, and other neurological symptoms and was found to have CJD on evaluation.


  Case Report Top


A 65-year-old female was admitted to our hospital with complaints of altered sensorium for 10 days, impaired speech for 1 week with the inability to recognize his family members and an inability to perform daily activities of living. He also had involuntary jerky limb movements for past 1 week. There is no history of loss of consciousness, fever, seizures, sensory disturbance, limb weakness, vomiting, loose stools, or abdominal pain. On probing further, his family members confirmed that he had memory loss, visual hallucinations, and clumsiness of movements for the past 6 months. He became progressively forgetful and dependent on others in daily activities. His general health had been good, and he had no history of any surgery or blood transfusion, injection of growth hormone, or contact with farm animals. He had no peculiar dietary preferences. There was no family history of neurological diseases.

On examination, she was confused and irritable and occasionally obeyed simple commands. The cranial nerves and sensory system were normal. Examination of the motor system revealed a generalized hypertonia and exaggerated deep tendon reflexes. Myoclonic jerks were present in both upper and lower limbs during the examination. He had no signs of meningeal irritation.

Investigations and workup

The patient underwent detailed clinical examinations to formulate differential diagnoses. No abnormalities were found in routine hematology, blood chemistry, syphilis, thyroid function, HIV, Vitamin B12, folic acid, ceruloplasmin, tumor markers screen, autoimmune screen, or cerebrospinal fluid (CSF) examination including CSF cultures. Nerve conduction studies were normal. Adenosine deaminase activity and polymerase chain reaction for tuberculosis were negative. Electroencephalograms (EEGs) revealed generalized slowing without repetitive complexes and poorly reactive slow background wake rhythms suggestive of an encephalopathy [Figure 1]. Magnetic resonance imaging (MRI) brain showed ribbon-like areas of cortical signal intensity, alternation on diffusion-weighted imaging (DWI), predominantly in parasagittal cortex and insular region on both sides. No signal intensity in basal ganglia and thalamus [Figure 2]. Fluorodeoxyglucose (FDG) and positron emission tomography MRI showed ribbon-like cortical signal alternation on DWI in bilateral frontoparietal and temporal lobes, predominantly the parasagittal and insular regions. Diffuse FDG hypometabolism involving bilateral cerebral hemisphere with relative sparring perirolandic region.
Figure 1: Electroencephalogram generalized slowing without repetitive complexes and poorly reactive slow background wake rhythms suggestive of an encephalopathy

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Figure 2: Magnetic resonance imaging brain showed ribbon-like areas of cortical signal intensity, alternation on diffusion-weighted imaging, predominantly in parasagittal cortex and insular region on both sides. No signal intensity in basal ganglia and thalamus

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Based on the history, examination, EEG, and MRI findings, we made a diagnosis of sporadic CJD. CSF 14-3-3 protein level could not be done due to nonavailability of the test in India. He was given intravenous immunoglobulin therapy for 5 days, supportive treatment, and anticonvulsants with physiotherapy. Patient gradually improved symptomatically and was discharged in a relatively stable condition with persistent memory impairment.


  Discussion Top


CJD is a rare, fatal neurodegenerative disease with distinctive clinical and pathological features. Sporadic CJD usually appears at 50–70 years of age consisting 90% of all cases with CJD. The diagnosis of sporadic CJD is based on clinical symptoms along with laboratory tests including an EEG, CSF, and serum analysis for specific proteins such as S-100 protein, Tau protein, 14-3-3 protein, imaging, and pathology. CJD can be sporadic, infectious, or familial with 80%–90% of cases being sporadic. The WHO criteria for probable sporadic CJD are:

  1. Exclusion of alternative diagnoses with routine investigations
  2. RPD
  3. At least two of the following four clinical features – myoclonus, visual disturbance or cerebellar dysfunction, pyramidal or extrapyramidal features, and akinetic mutism
  4. A typical EEG pattern (periodic sharp wave complex) and/or CSF positive for 14-3-3 protein by immunoblot
  5. A clinical duration of <2 years before death.[6]


The classical diagnostic presentation of CJD is a rapid cognitive decline with visual, cerebellar, pyramidal, or extrapyramidal signs, myoclonus, and abnormalities on EEG or diffusion-weighted MRI. The mean duration of illness is 4.5 months.[7]

There are three different stages of the disease during its clinical evolution:





  1. Prodrome – In this stage, the patient presents with vague symptoms such as asthenia, depression, sleep disorders, inattention, weight loss, visual complaints/abnormalities, motor incoordination, and nystagmus. This stage lasts about 3–4 months
  2. Disease stage – Symptoms of progressive dementia, behavioral disorders, cognitive compromise, as well as clinical signs of pyramidal, extrapyramidal, and cerebellar compromise, as well as those of a lower motor neuron disease comprise the clinical picture. This has a mean duration of 4–5 months
  3. Terminal stage – In this end-stage phase, the patient progresses to coma with myoclonic jerks, further evolving to abnormal decortication and decerebration postures, seizures, and dysautonomic symptoms. The duration varies according to the nursing care administered to the patient.[8]


The clinical features of CJD can sometimes be seen in mimics for CJD including Alzheimer's disease (AD) and less commonly dementia with Lewy bodies (DLBs). Neither AD nor DLB has the EEG or MRI changes seen in CJD.[9] EEG studies play an important role in the investigation and diagnosis of CJD when specific findings are found, thus allowing the clinician to progress in the investigation from a suspected case of CJD to a probable diagnosis status, which also has epidemiological repercussions.[10] Typical EEG findings of CJD are generalized complexes, either biphasic or triphasic, lasting for 100–300 ms, with a mean amplitude of 300 μV and an interval among repetitions of 0.5–1.5 s.[10],[11] May proposed, in 1968, a clinical staging for the disease, with a good correlation with EEG evolution.[12] In the prodromic phase, the clinical symptoms are somewhat vague such as headache, vertigo, confusion, and syncope. In this stage, the EEG shows a slowing of background activity, with both theta and delta waves with a generalized bilateral distribution, sometimes predominating over one hemisphere or the other. Furthermore, physiological sleep graph elements are lacking.[10],[11]

Myoclonic jerk may be seen in various conditions such as vascular, infectious, hypoxic, metabolic, degenerative, paraneoplastic, or autoimmune disease.[13] Cognitive decline and myoclonus can be present in subacute sclerosing panencephalitis and neurosyphilis, and some autoimmune disease such as Hashimoto's encephalitis. However, our patient's blood screening and CSF examination results were all negative, ruling out these disorders listed.[14] Patients with hypoxic encephalopathy and adult-onset lipid-storage diseases may mimic the symptoms, but our patient did not have the histories of these diseases. Mild myoclonus may occur in AD but with a slow clinical course.[15] However, our patient had a rapid clinical course.


  Conclusion Top


CJD is a progressive neurological condition with fatal outcome. The early features of CJD vary and are nonspecific. Our patient's clinical presentation and EEG findings provided clues for diagnosis according to the WHO CJD criteria.[6] MRI of the brain in the early stages may give the clinician a hint to be aware of the possibility of CJD, although it is not included in diagnostic criteria. It is important for physicians to be cognizant of the clinical and investigative features of CJD to make a differential diagnosis. Early diagnosis is still a challenge in the early stages of CJD.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Geschwind MD, Haman A, Miller BL. Rapidly progressive dementia. Neurol Clin 2007;25:783-807, vii.  Back to cited text no. 1
    
2.
Papageorgiou SG, Koros C. Rapidly progressive dementia – Clinical aspects and management. Eur Neurol Rev 2011;6:238-45.  Back to cited text no. 2
    
3.
Jakob A. Concerning a disorder of the central nervous system clinically resembling multiple sclerosis with remarkable anatomic findings (Spastic pseudosclerosis). Report of a fourth case. Alzheimer Dis Assoc Disord 1989;3:26-45.  Back to cited text no. 3
    
4.
Creutzfeldt HG. On a particular focal disease of the central nervous system (preliminary communication), 1920. Alzheimer Dis Assoc Disord 1989;3:3-25.  Back to cited text no. 4
    
5.
Johnson RT. Prion diseases. Lancet Neurol 2005;4:635-42.  Back to cited text no. 5
    
6.
World Health Organization. Global Surveillance, Diagnosis and Therapy of Human Transmissible Spongiform Encephalopathies: Report of a WHO Consultation. (WHO/EMC/ZOO/97.3). Geneva: WHO; 1998.  Back to cited text no. 6
    
7.
Bosque PJ, Tyler KL. Prions and prion diseases of the central nervous system (Transmissible Neurodegenerative Diseases). In: Bennett JE, Dolin R, Blaser MJ, editors. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Philadelphia: Elsevier; 2015.  Back to cited text no. 7
    
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Yasuda N, Scaff M. Creutzfeldt-Jakob disease and Bovine Spongiform Encephalopathy. In: Transmissible Spongiform Encephalopathy: Notebook Técnicolish. 1st ed. Brasília: National Health Surveillance Agency (ANVISA); 2004.  Back to cited text no. 8
    
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World Health Organization. WHO Manual for Surveillance of Human Transmissible Spongiform Encephalopathies Including Variant Creutzfeldt – Jakob Disease. Geneva, Switzerland: World Health Organization; 2003.  Back to cited text no. 9
    
10.
Ortega-Albás JJ, Serrano-García AL. Neurophysiology in Creutzfeldt-Jakob disease. Rev Neurol 2003;36:376-80.  Back to cited text no. 10
    
11.
Markand ON. Organic brain syndromes and dementias. In: Daly DD, Pedley TA, editors. Current Practice of Clinical Electroencephalography. New York: Rave Press; 1990. p. 413-5.  Back to cited text no. 11
    
12.
May WW. Creutzfeldt-Jakob disease 1. Survey of the literature and clinical diagnosis. Acta Neurol Scand 1968;44:1-32.  Back to cited text no. 12
    
13.
Sadowski M, Verma A, Wisniewski T, Bradley WG, Daroff RB, Fenichel G, et al. Infections of nervous system: Prion diseases. In: Neurology in Clinical Practice. 5th ed. USA: Butterworth-Heinemann; 2008. p. 1567-81.  Back to cited text no. 13
    
14.
See SJ, Pan A, Seah A, Teo J, Chan LL, Wong MC, et al. Case reports of two biopsy-proven patients with Creutzfeldt-Jakob disease in Singapore. Ann Acad Med Singapore 2004;33:651-5.  Back to cited text no. 14
    
15.
Heinemann U, Gawinecka J, Schmidt C, Zerr I. Differential diagnosis of rapid progressive dementia. Eur Neurol Rev 2010;5:21-8.  Back to cited text no. 15
    


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