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Table of Contents
Year : 2021  |  Volume : 9  |  Issue : 2  |  Page : 125-127

Rapidly progressive dementia: Clue lies in the speed of progression

1 Department of General Medicine, Srimathi BK Shah Medical Institute and Research Centre, Vadodara, Gujarat, India
2 Department of Neurology, Srimathi BK Shah Medical Institute and Research Centre, Vadodara, Gujarat, India

Date of Submission19-Jun-2021
Date of Decision03-Nov-2021
Date of Acceptance28-Nov-2021
Date of Web Publication15-Mar-2022

Correspondence Address:
Dr. Ande Jeevana Sudha
Room No. 16, VAMA Girls Hostel, Sumandeep Vidyapeeth, Pipariya, Vadodara - 391 760, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jihs.jihs_20_21

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Dementia is one of the most common neurological manifestations. While degenerative dementia is the commonest form of dementia, various metabolic, toxic, infective, and inflammatory diseases can also present with dementia. It is the course of the disease, speed of the progression, and the presence of associated features which often give clue to the diagnosis of nondegenerative dementias. Here, we report a case of rapidly progressive dementia in a middle-aged male patient and discuss the various differential diagnoses.

Keywords: Dementia, prion disease, rapid progression

How to cite this article:
Sudha AJ, Rathore C, Kumar S, Yeeli G. Rapidly progressive dementia: Clue lies in the speed of progression. J Integr Health Sci 2021;9:125-7

How to cite this URL:
Sudha AJ, Rathore C, Kumar S, Yeeli G. Rapidly progressive dementia: Clue lies in the speed of progression. J Integr Health Sci [serial online] 2021 [cited 2023 Mar 29];9:125-7. Available from: https://www.jihs.in/text.asp?2021/9/2/125/339648

  Introduction Top

Prion diseases have an incidence of 1per million population and accounts for one in every10000 deaths in the world affecting age group of 55–70 years. Prions are proteins of unknown function in human genome encoded by PrP (PRNP) located on Chromosome20. In this disease, PrP prions reproduce by binding to normal, cellular isoform of prion protein (PrPC) and activate conversion of PrPc into PrPSC isoform leading to degeneration of brain tissue. Clinical features include rapidly progressive memory loss, impaired judgment, decline in intellectual function which progress rapidly over months ultimately leading to death. Other features include myoclonus, visual disturbances, rigidity, cerebellar, pyramidal and extrapyramidal signs.[1]

  Case Report Top

A 40-year-old right-handed male presented with complaints of forgetfulness since 1 year. The patient initially had a loss of recent memory which progressed to difficulty in recognition of family members, anomia, and prosopagnosia leading to advanced dementia and akinetic mutism over 1 year. In addition, he also developed urinary incontinence, two episodes of generalized tonic-clonic seizures, progressive gait ataxia, and became bedridden within a span of 8–9 months. There was no fever, headache, vomiting, systemic symptoms, visual disturbances, skin lesions, and photosensitivity. There was no past history of major illness or stroke-like episodes. On examination, he was vitally stable. He had proximal and distal myoclonus. He was mute with the rigidity of all four limbs. Deep tendon reflexes (DTR) was brisk and plantars were extensors. Fundus and other system examinations were normal. On investigation complete blood count, (CBC), renal function test (RFT), liver function test (LFT), thyroid and antithyroid antibodies, Vitamin B1, B12 were normal. Cerebrospinal fluid (CSF) analysis showed 2 cells, with protein and sugar level of 45 mg% and 68 mg%. No autoimmune antibodies including anti-N-methyl-d-aspartate, anti voltage gated potassium channelcomplex, anti glutamic acid decarboxylase were detected in CSF. Magnetic resonance imaging (MRI) brain showed multifocal, poorly defined, hyperintense signals in bilateral caudate, anterior part of lentiform nuclei, bilateral insular cortices, anterior temporal lobes, frontal and occipital lobes on fluid-attenuated inversion recovery and diffusion-weighted imaging [Figure 1]a. Serial MRI showed progressive cerebral atrophy in frontal and temporal lobes, focal gliosis of right occipital lobe, and multifocal bilaterally symmetrical abnormal signal intensity in cortical-subcortical location of anterior parts of bilateral frontotemporal lobes with decrease in volume and dilatation of adjacent sulci and ventricles [Figure 1]b. Electroencephalography (EEG) suggestive of generalized, short interval, periodic discharges with a moderately severe degree of background slowing [Figure 2]. With these MRI and EEG findings, a possibility of Creutzfeldt Jacob disease (CJD) was considered. A brain biopsy was done to confirm diagnosis which showed cortical atrophy and spongiform vacuolation suggestive of CJD.
Figure 1: (a) Axial fluid attenuated inversion recovery image showing patchy hyper-intensities in bilateral anterior temporal lobes, insular cortex (arrows) and basal ganglia; (b) Subsequent T2W axial image after 4 months shows generalized atrophy with dilatation of the ventricles

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Figure 2: Electroencephalography showing generalized, 1 Hz, short interval period discharges (sensitivity: 10 microvolt/mm; high frequency filter: 70 Hz: low frequency filter: 1 Hz)

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  Discussion Top

It is the course of the disease, speed of the progression, and the presence of associated features which often give clue to the diagnosis of nondegenerative dementias.

Questions and differential diagnosis:

  1. In the given clinical context, what are the differential diagnoses?
  2. What investigations will help us in confirming the diagnosis?

In a patient presenting with nonlocalizing (no focal neurological signs) rapidly progressive dementia following differential diagnosis are usually considered:

Metabolic/toxic encephalopathy: While most metabolic disturbances usually present with acute or subacute encephalopathy, certain metabolic/toxic encephalopathies have a chronic course. Hyperammonemia due to chronic liver disease can present with chronic encephalopathy and dementia. Similarly, B12 deficiency can present with chronic dementia, lead toxicity and chronic aluminium toxicity (while on haemodialysis) can present with rapidly progressive dementia. Blood investigations including CBC, RFT, LFT, electrolytes, B12 levels, and toxicological screening help to rule out these diagnoses.[2] Chronic viral/bacterial meningitis: Chronic meningitides such as tubercular and fungal infections,  Brucellosis More Details can present with subacute and chronic encephalopathy. However, these patients have fever, headache, and vomiting as presenting features while encephalopathy develops later. Examination of CSF for detection of various organism is essential if chronic meningitis is suspected.[3] Autoimmune encephalitis: Although majority of autoimmune encephalitides have a subacute course, some of them especially Hashimoto's and limbic encephalitis can present with rapidly progressive dementia and seizures. They usually present with behavioural and psychiatric disturbances, movement disorders, and seizures which progresses to altered sensorium. A combination of clinical features, MRI findings, CSF examination for specific autoimmune antibodies, and EEG helps in confirming diagnosis. However, in many cases, a positive diagnosis cannot be made and diagnosis depends on exclusion of other conditions.[4] Inflammatory diseases: Vasculitis and sarcoidosis can present with rapidly progressive neurological deterioration. These patients usually have subacute course, focal neurological disturbances, multiple cranial nerve palsies, and systemic symptoms. A combination of clinical and MRI features helps to reach a diagnosis.[5] Degenerative dementia: These diseases have chronic indolent course progressing for many years. Rapid progression is not a feature of these diseases. Occasionally, a patient of degenerative dementia can deteriorate more acutely due to systemic factors like fever. These patients usually return to baseline once underlying cause is corrected.[6] CJD: CJD manifests with rapidly progressive mental deterioration with variable neurological features leading to death within few months of symptoms usually affecting 55–70 years people. It presents with rapidly developing dementia, myoclonus, generalized seizures, and other neurological deficits. Diagnosis is based on clinical suspicion and is confirmed by EEG and MRI features and occasionally with brain biopsy.[7] It has four different forms: (1) sporadic(s) (mostcommon); (2) familial, (3) iatrogenic, and (4) variant(v). CJD is considered transmissible by PrPSC protein via blood transfusions, needlestick injuries, dental and surgical procedures. Although nature of infectivity is still not known, it should not be considered contagious or communicable. Two main subtypes of CJD are (1) sCJD: Age of onset is 60–70 years, with a rapid clinical progression leading to death within one year of symptom onset. The mechanism of spontaneous neurodegeneration is either PRNP gene mutation or structural change in prion protein. Typical MRI and EEG findings are seen in about 60%–70% of cases. CSF 14-3-3 is positive in about 90% of cases; (2) VCJD: It is associated with consumption of beef products affecting 28 years age group. Psychiatric symptoms predominate than cognitive impairment. Pulvinar sign is seen on MRI (90%cases) with absent typical EEG findings. CSF 14-3-3 is positive (50%cases).[8] The WHO diagnostic criteria for sCJD include Progressive dementia and at least two out of the following (1) Myoclonus; (2) Visual/cerebellar disturbance; (3) Pyramidal/extrapyramidal dysfunction; (4) Akinetic mutism and a typical EEG during any duration of illness or a positive 14-3-3CSF assay and a clinical duration to death <2 years; (5) Routine investigation should not suggest an alternative diagnosis; (6) Detection high signal intensity from basal ganglia on T2 and proton density-weighted MRI.[9] Typical MRI findings of high signal intensities in basal ganglia can be seen in about 80% of cases and typical EEG findings of periodic sharp wave complexes can be seen in about 60% of cases.[10]

Our case was diagnosed probably as CJD according to the diagnostic criteria of WHO as our patient met the criteria of rapidly progressive dementia within a span of 6 months, myoclonus, akinetic mutsim, rigidity with typical EEG and MRI findings. The diagnosis was further supported by brain biopsy which showed spongiform vacuolation and cortical atrophy which adds to the diagnosis of probability of CJD. A confirmatory diagnosis needs genetic testing for PRNP gene or RTQUIC testing.

Unfortunately, there are no preventive and treatment strategies to combat this transmissible CJD. Palliative care is the only treatment option for CJD, it should be differentiated from other causes of dementia which can be treated.

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 guarantee.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Knight R. Creutzfeldt-Jakob disease: A rare cause of dementia in elderly persons. Clin Infect Dis 2006;43:340-6.  Back to cited text no. 1
Sahoo S, Pearl PL. Korsakoff Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:546  Back to cited text no. 2
Long SS. Encephalitis diagnosis and management in the real world. Adv Exp Med Biol 2011;697:153-73.  Back to cited text no. 3
Lancaster E. The diagnosis and treatment of autoimmune encephalitis. J Clin Neurol 2016;12:1-13.  Back to cited text no. 4
Kramer J, Seeley WW, Miller BL. Vascular dementia. In: Harrison's Principles of Internal Medicine. 20th ed. McGraw Hill; New York 2018. Part 13. 20th ed., Vol. 2, p. 3118.  Back to cited text no. 5
Poser S, Mollenhauer B, Kraubeta A, Zerr I, Steinhoff BJ, Schroeter A, et al. How to improve the clinical diagnosis of Creutzfeldt-Jakob disease. Brain 1999;122:2345-51.  Back to cited text no. 6
Prusiner SB, Miller BL. Prion diseases. Harrison's Principles of Internal Medicine. 20th ed. McGraw Hill; New York 2018. Part 13. 20th ed., Vol. 2, p. 3152.  Back to cited text no. 7
Manix M, Kalakoti P, Henry M, Thakur J, Menger R, Guthikonda B, et al. Creutzfeldt-Jakob disease: Updated diagnostic criteria, treatment algorithm, and the utility of brain biopsy. Neurosurg Focus 2015;39:E2.  Back to cited text no. 8
Unit B, World Health Organization, World Health Organization. Report of a WHO Consultation on Medicinal and other Products in Relation to Human and Animal Transmissible Spongiform Encephalopathies, Geneva, Switzerland, World Health Organization; 1997.  Back to cited text no. 9
Mackenzie G, Will R. Creutzfeldt-Jakob disease: Recent developments. F1000Res 2017;6:2053.  Back to cited text no. 10


  [Figure 1], [Figure 2]


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