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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 2  |  Page : 175-180

Beware of the cortical ribboning: The spectrum – Experience from a case series


1 Department of Neurology, Faculty Block, Neurocentre, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
2 Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
3 Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
4 Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
5 Department of Radiology and Imaging, Neurocentre, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

Date of Submission17-Jun-2019
Date of Decision18-Jan-2020
Date of Acceptance28-Jan-2020
Date of Web Publication9-Apr-2020

Correspondence Address:
Sadanandavalli Retnaswami Chandra
Department of Neurology, Natonal Institute of Mental Health and Neurosciences, Bengaluru - 560 029, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijhas.IJHAS_49_19

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  Abstract 


INTRODUCTION: Creutzfeldt–Jakob disease (CJD) is an uncommon, fatal, genetic, transmissible and degenerative, brain disorder. It affects one person in every one million in the United States. A definite diagnosis can be made by histopathological confirmation which is often not possible for various reasons. Therefore, great caution is needed before the diagnosis is offered.
MATERIALS AND METHODS: Patients with radiological diagnosis of CJD in the past 2 years were assessed clinically, reassessed at 1-month, and results are discussed.
RESULTS: Four out of the 12 patients seen had nonprion cause. Hyperacute onset with coma, nonprogressive changes in imaging and electroencephalography, were seen in those who improved. The presence or absence of 14-3-3 in cerebrospinal fluid was not useful in either confirming or excluding the diagnosis in a given case.
CONCLUSION: All patients with cortical ribboning need correlation with clinical features and follow-up to confirm or exclude prion disease.

Keywords: Cortical ribbon, Creutzfeldt–Jakob disease, nonprion disease


How to cite this article:
Chandra SR, Gohel A, Mallikarjuna SD, Gangadhar KB, Subramanian S, Bhat MD. Beware of the cortical ribboning: The spectrum – Experience from a case series. Int J Health Allied Sci 2020;9:175-80

How to cite this URL:
Chandra SR, Gohel A, Mallikarjuna SD, Gangadhar KB, Subramanian S, Bhat MD. Beware of the cortical ribboning: The spectrum – Experience from a case series. Int J Health Allied Sci [serial online] 2020 [cited 2020 May 30];9:175-80. Available from: http://www.ijhas.in/text.asp?2020/9/2/175/282137




  Introduction Top


Cortical ribboning is the term given to an imaging appearance characterized by hyperintense signal changes seen in cerebral cortex and basal ganglia in diffusion-weighted magnetic resonance imaging (MRI). This appearance is postulated to be related to severe rapid neuronal loss in prion disease, hypoxia, hypoglycemia, anemia, and status epilepticus. In acute situations, an important imitator is Wernicke's encephalopathy. Thalamus, perirolandic region, and mammillary body involvement is seen along with restriction in diffusion-weighted images (DWI). During serial follow-up, there is cortical enhancement after 2 weeks. This is followed by T1 hyperintensities by 1 month, and the whole change disappears by 8 months.

Cortical ribboning is a sensitive marker of Creutzfeldt–Jakob disease (CJD) even in cases which are genetically negative but pathologically confirmed.[1] According to the WHO criteria, a typical electroencephalography (EEG) and/or a positive 14-3-3 cerebrospinal fluid (CSF) assay are necessary for the diagnosis.[2] Cortical layers 3, 4, and 5, primary visual cortex and perirolandic cortex are especially vulnerable to metabolic stress due to more demand and presence of more receptors for excitatory amino acids that are released after an anoxic-ischemic event.[3],[4],[5],[6] The course of the illness and pattern will give a clue to probable cause. Cingulum, superior frontal cortex, and insula are commonly involved in sCJD.[1]

Hans Gerhard Creutzfeldt (1887–1964) in 1920 and Alfons Jakob (1884–1931) described rapidly progressive dementias and termed them as “Spastic pseudo sclerotic encephalopathy” with disseminated foci of degeneration.[7] Spiel Meyer (1922) coined the term “Creutzfeldt–Jakob” which turned out to be spongiform encephalopathy.[8] Daniel Carleton Gajdusek demonstrated its transmissible nature.[9] Tikvah Alper, Ian Pattison postulated that it did not contain nucleic acid. Stanley Prusiner called it as proteinaceous infectious particle.[10] Six genotypes – MM1, MM2, MV1, MV2, VV1, and VV2 are described based on methionine (M) and valine (V) heterozygosity at residue 129 in the prion protein gene. From India, various authors have described their experience with this fatal disease.[11],[12] The analysis of CSF shows elevated protein <100 mg/dl as well as markers such as 14-3-3, S100 β, neuron-specific enolase (NSE), and total tau (t-tau). A sensitivity of the 14-3-3 (>2 ng/ml) by Western blot in the literature ranges from 53% to 97%. T-tau (>1200 pg/ml) has higher diagnostic accuracy than NSE (>30 ng/ml) or 14-3-3, but DWI/apparent diffusion coefficient (ADC) MRI has much higher accuracy than any or all of these three biomarkers (97% for MRI vs. 70%–80% for biomarkers).[13],[14] A real-time quaking-induced conversion detects prions by amplifying them into amyloid fibrils, with sensitivity of about 77%–92% and specificity 99%–100%. Once the diagnosis is confirmed, there is severe morbidity and mortality. Therefore, it is important to identify the imitators as it means life from death for the patients. In this study, we describe our experiences with this unique radiological sign.


  Materials and Methods Top


The patients who were referred to us in the past 2 years with the radiological diagnosis of CJD and came for 2nd opinion to our team were evaluated with a thorough history, clinical examination in detail which included evaluation of activities of daily living, behavior, cognition and detailed neurological evaluation. All of them underwent all dementia mandatory work up in the form of complete blood count, B12, thyroid function test, vasculitic workup, HIV, homocysteine, liver function, renal function, electrolytes, lipid profile and also vasculitic work up, CSF for routine examination, chronic infection workup, and screening for 14-3-3 in CSF in few cases. EEG and MRI (T1, T2, DWI) were done in all cases. EEG was repeated after 2 weeks in patients who did not show typical features. MRI was repeated in patients who were atypical at 1–3 months and for survivors at 1-year.


  Results Top


We had 12 cases seen in the past 2 years with a referral diagnosis of CJD. There were 7 males and 5 females [Table 1]. The age group varied from 24 years to 73 years. Autoimmune workup and paraneoplastic workup was negative in all cases. Four patients out of twelve patients survived. Eight patients deteriorated or died. The mean age of the survivors was 48 years and those who deteriorated or expired was 57.8 years. Among survivors, there was only one female and 3 males (25% vs. 75%) and among those who deteriorated or expired, the gender distribution was 50% each. The presenting feature among survivors was coma in 3 cases and cerebral blindness in one case. In the deteriorated group, delirium was seen in 7 cases, visual symptoms in 5 cases. Basal ganglia features were seen in all survivors and 5 out of 8 of the progressive cases. EEG showed periodic complexes in one out of four of the survivors and the rest showed varying changes such as slowing, mid-positive triphasic waves, and frontal intermittent rhythmic delta activity whereas in the other group EEG showed classical features in 6 and other 2 showed nonspecific changes. MRI showed cortical ribboning in all cases and basal ganglia features evolved in all cases who progressed but in the cases which reversed two patients had complete radiological features (cortical ribboning and basal ganglia changes) and other two had only cortical ribboning and did not progress during the follow-up. 14-3-3 was done in only 3 cases and was positive in one patient in the reversible group and negative in two patients who progressed. Morbidity was severe in both groups but mortality at varying periods during follow-up happened in 6 out of 8 cases who showed progressive changes and other 2 in this group became bed-bound one at 4 months and the other patient at 9 months [Table 1] shows demographic and clinical features. [Table 2] shows initial symptoms and outcome]. The surviving group showed very good improvement during follow-up both clinically as well as by investigations (EEG and MRI) [Figure 1]a, [Figure 1]b, [Figure 1]c shows MRI changes, [Figure 1]d shows EEG and [Figure 1]e shows 14-3-3 in a typical survivor. [Figure 2] MRI and EEG in a typical patient who deteriorated. [Figure 3] MRI and EEG in A recovered case].
Table 1: Demographic and clinical features

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Table 2: Initial symptoms versus out come

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Figure 1: (a-c) Apparent diffusion coefficient, fluid attenuated inversion recovery and diffusion Images of case 1 who completely reversed before treatment and after treatment. (d and e) electroencephalography of case 1 before and after treatment and weak positive 14-3-3 in case 1

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Figure 2: (a and b) Show cortical ribboning. (c) EEG showing one/second sharp waves in a classical case of CJD

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Figure 3: (a and b) Shows MRI features remaining unchanged in a case of non CJD cortical ribboning. (c) EEG showing features of metabolic encephalopathy in the same case

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Sample case 1

A 61-year-old female presented with restlessness and increased frequency of micturition and wandering of 2 weeks' duration. She would try to communicate with persons who were not there and would not attend to persons in front of her. She would search for steps with her legs and explore space with hand. She had no vision but pupil and fundus were normal suggesting cortical blindness. She was poorly attentive and not cooperative for neuropsychological tests. She did not have any other focal neurological deficits or myoclonic jerks. She deteriorated fast and became incontinent. She had undergone arthroscopic evaluation of knee joint but did not give a history of transplants, hormone injections, intracranial surgery, blood transfusion, etc., There was no family history of any similar or serious diseases. She had microcytic hypochromic anemia with mild anisocytosis. Her CSF analysis showed 25 cells which were all lymphocytes. India ink for cryptococci and cryptococcal antigen was negative. CSF protein was elevated (147 mg/dl). Real-time polymerase chain reaction for herpes simplex virus-1 DNA, John Cunningham virus DNA, chikungunya viral RNA negative, Pan enteroviral RNA, dengue RNA, IgM antibody against Japanese Encephalitis, IgG antibody to measles negative. CSF 14-3-3 protein showed weak signal by immunoblotting method (polyclonal antibodies to recombinant 14-3-3 protein fragment) suggesting nerve cell loss [Figure 1]e. Her EEG showed mid-positive triphasic waves which were recurrent at irregular intervals [Figure 1]d. Her MRI brain done with DWI, fluid-attenuated inversion recovery (FLAIR), ADC showed cortical signal changes in DWI across bilateral frontal, cingulum, parietal regions and were less prominent in FLAIR and hypointense in ADC in the same regions. There was hyperintensity in both pulvinars right more than left consistent with cortical ribboning [Figure 1]a-c shows ADC, DWI, FLAIR before and after treatment]. She satisfied the criteria for probable CJD of Heidenhain variant. The family was counseled and the patient was discharged with treatment for her comorbidities and flupirtine 200 mg daily. Our patient is on regular follow-up from November 2016 and her last follow-up was in March 2018. The patient was followed up every 6 months and she slowly showed signs of improvement. She is currently fully independent for activities of daily living and has returned to her usual household work. Her MRI and EEG showed a complete reversal of all abnormalities. Her recovery and cause remain unexplained.

Sample case 2

A 73 -year-old female presented with visual disturbances in the form of difficulty in negotiating familiar places for 14 days which was rapidly deteriorating, followed by behavioral changes in the form of hallucinatory behavior, clapping, laughing, and insisting on wearing ornaments followed by jerky movements of upper limbs and stupor. Her MRI showed cortical ribboning involving frontal regions, cingulum, and temporal regions [Figure 2]a. Repeat MRI done after 3 weeks showed pulvinar sign and inverted hockey stick sign [Figure 2]b. EEG showed 1–1.5 Hz sharp waves periodic complexes and MRI repeated at admission showed progression to basal ganglia [Figure 2]b. The patient deteriorated very fast and passed away at her residence within 2 months.

Case 3

A 55-year-old alcoholic had a binge drinking in February 2018, following which he was drowsy for 1 day. Then, he was searching for objects, unable to localize rooms inside his house, unable to recognize faces, familiar objects, was entering into houses of neighbor's, was disinhibited and incontinent. At admission with the diagnosis of CJD, he was in locked-in state. His MRI showed cortical ribboning involving parieto-occipital region [Figure 3]a and EEG showed features of Grade 3 metabolic encephalopathy [Figure 3]c. Blood parameters suggested albumin globulin reversal and elevated bilirubin suggesting alcoholic liver disease. MRI repeated at 3 months showed no progression [Figure 3]b. He was treated with liquid L-dopa with carbidopa 1.25 g dissolved in 1 liter of distilled water given 15 ml every 30 min with laxative, thiamine, and supportive measures. The patient showed dramatic improvement in 10 days' time and was discharged in stable condition.


  Discussion Top


Although cortical ribboning is described in a wide variety of situations, the unique combination of rapidly progressive dementia, cortical blindness, typical EEG, CSF 14-3-3, and no other demonstrable cause as well as the presence of pulvinar sign satisfies the criteria for probable sCJD. Studies have revealed that DWI sequences can even predict a rapid deterioration when both cortical ribboning and basal ganglia changes are seen. Patients who showed changes in only in FLAIR may need investigation for alternate causes pulvinar sign is reported to have a sensitivity of 78% and specificity of 100% for the diagnosis of variant CJD. The female patient who deteriorated very fast in weeks remitted completely. Her diagnosis remains to be answered. The other three patients who survived were diagnosed CJD elsewhere based on radiological features but they had alcoholic drink, were comatose, and did not show progressive changes in MRI or EEG. The patients who showed progressive changes in MRI and EEG deteriorated, 6 out of 8 expired and two patients were surviving in bed-bound stage, one at 4 months and another at 9 months. No further follow-up is available of these two patients. This study gives a definite message that all patients who show cortical ribboning in situ ations of encephalopathy do not suffer from CJD. The radiology has to be correlated with clinical features whenever there was a doubt or the ribboning was seen only in FLAIR and not in DWI sequences. The other features to be observed are in atypical cases, follow-up EEG and MRI are very important and if no progression is seen, it is less likely to be CJD.


  Conclusion Top


We report patients who satisfied radiological criteria for probable CJD and were followed up for 6 months–2 years clinically, radiologically, and electrophysiologically. Four out of the twelve patients improved considerably indicating they are nonprion disease. Several questions need to be answered which include whether the whole features – clinical, radiological, EEG, CSF seen at one time qualify for the diagnosis of PRION disease without histopathological confirmation. What are the potentially unknown reversible disorders which can produce these features? Male gender, younger age group, coma at onset and alcoholism if present, follow-up EEG and MRI are needed. If it remains stable, they are likely to be mimics. Unstable progressive imaging and EEG changes, delirium at onset, rapid deterioration older age group is likely to be probable CJD. Great caution is needed in giving diagnosis when pathological confirmation is not done in view of the fatal nature of the diagnosis. The questions can be answered by future observation of more such cases and histopathological confirmation when possible.

Limitation

Histopathological confirmation not done in any of the patients in view of the risk of transmission.

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.

Acknowledgment

We would like to acknowledge with gratitude the patients, caregivers, and the Director National Institute of Mental Health and Neuro Sciences for the kind cooperation for this learning opportunity.



Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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World Health Organization. Global Surveillance, Diagnosis and Therapy of Human Transmissible Spongiform Encephalopathies: Report of a WHO Consultation. Geneva, Switzerland: World Health Organization; 1998.  Back to cited text no. 1
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

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