Heidenhain Variant Of Creutzfeldt-Jakob Disease Research Articles

Clinical and Genetic Characteristics of the Heidenhain Variant of Creutzfeldt-Jakob Disease.

The Heidenhain variant of Creutzfeldt-Jakob disease (HvCJD), as a rare phenotype of CJD, has been under-recognized. We aim to elucidate the clinical and genetic features of HvCJD and investigate the differences of clinical features between genetic and sporadic HvCJD to improve our understanding of this rare subtype. HvCJD patients admitted to the Xuanwu Hospital from February 2012 to September 2022 were identified, and published reports on genetic HvCJD cases were also reviewed. The clinical and genetic features of HvCJD were summarized, and the clinical features between genetic and sporadic HvCJD were compared. A total of 18 (7.9%) HvCJD patients were identified from 229 CJD cases. Blurred vision was the most common visual disturbance at the disease's onset, and the median duration of isolated visual symptoms was 30.0 (14.8-40.0) days. DWI hyperintensities could appear in the early stage, which might help with early diagnosis. Combined with previous studies, nine genetic HvCJD cases were identified. The most common mutation was V210I (4/9), and all patients (9/9) had methionine homozygosity (MM) at codon 129. Only 25% of cases had a family history of the disease. Compared to sporadic HvCJD, genetic HvCJD cases were more likely to present with non-blurred vision visual symptoms at onset and develop cortical blindness during the progression of the disease. HvCJD not only could be sporadic, but also, it could be caused by different PRNP mutations. Sporadic HvCJD was more likely to present with blurred vision visual symptoms at onset, and genetic HvCJD was more likely to develop cortical blindness with the disease's progression.

When vision loss is beyond cataract: a case of fatal neurodegenerative disease (P1-9.010)

<h3>Objective:</h3> NA <h3>Background:</h3> Creutzfeldt Jakob disease (CJD) is a rare and fatal neurodegenerative disorder of unclear etiology. Presentation include myoclonic jerks, visual disturbances, pyramidal/extrapyramidal signs and rapidly progressive cognitive decline. Visual symptoms are a common manifestation of CJD. Here we present a case of progressive vision loss initially attributed to cataract with eventual diagnosis of CJD. <h3>Design/Methods:</h3> Patient is a 75-year-old woman with history of osteoporosis, dyslipidemia, and arthritis presented to the emergency (ED) with bilateral vision loss and cognitive decline. Symptoms started 8 weeks prior presentation with progressive vision loss and difficulty recognizing color and shapes. She also had intermittent horizontal diplopia. Patient was initially evaluated by an ophthalmologist where vision loss was attributed to cataract and underwent bilateral cataract extraction with no improvement in vision. Vision loss worsened and she became unable to recognize familiar faces or identify objects, and had recurrent falls. She suffered visual hallucination, progressive abnormal body posturing, memory loss, dysphagia and severe dysarthria. On her exam she was noted to be mute, unable to follow commands, and had stimulus induced myoclonic jerks of limbs. CXR, urine analysis, urine and blood cultures, and urine drug screen were all unrevealing. Serum and CSF paraneoplastic panel were negative. EEG showed absence of the posterior dominant rhythm. Brain MRI demonstrated cortical ribbon sign and hyperintensities of basal ganglia (image 1). CSF Rt-Quic was indeterminate. Given the history, exam and MRI findings, she was diagnosed with Heidenhain variant of CJD and passed away shortly after transfer to inpatient hospice. <h3>Results:</h3> NA <h3>Conclusions:</h3> CJD can present with isolated visual symptoms that precede cognitive decline by weeks. Detailed history and careful exam are essential for early diagnosis as this will allow patients and their families to prepare for the expected disease course, consider goals of care, and possibly have palliative care if desired. <b>Disclosure:</b> Dr. Abusamra has nothing to disclose. Dr. Ali has nothing to disclose. Dr. Sudhakar has nothing to disclose.

Clinical and prognostic features of Heidenhain variant of Creutzfeldt−Jakob disease: A retrospective case series study

Heidenhain variant of Creutzfeldt-Jakob disease (CJD) remains a diagnostic challenge in clinical practice. We aimed to describe the clinical and prognostic features of Heidenhain cases, through a case series study. We retrospectively reviewed the definite or probable CJD cases admitted to two tertiary referral university hospitals over a decade to identify Heidenhain cases and investigated their survival status by telephone follow-up. Their clinical characteristics, neuroimaging features, electroencephalography (EEG) results, cerebrospinal fluid profiles, and PRNP gene mutations were also analyzed. Of a total of 85 CJD cases, 20 (24%) Heidenhain cases (11 women [55%]; median age, 64years [range, 44-72years]) were identified. The median survival time was 22weeks (range, 5-155weeks). The median duration of isolated visual symptoms was 3weeks (range, 1-12weeks). The most common early visual symptom was blurred vision (16/20, 80%), followed by diplopia (6/20, 30%). The prevalence significantly increased for complex visual hallucination (p=0.005) and cortical blindness (p=0.046) as the disease progressed. The positive rate of serial magnetic resonance images (20/20, 100%) was higher than that of serial EEGs (16/20, 80%). Two patients (2/10, 20%) had pathogenic PRNP mutations, E196A and T188K, respectively. Heidenhain cases with PRNP mutations had significantly longer survival time than those without PRNP mutations (p=0.047). Besides blurred vision (80%), diplopia (30%) was also a frequent early visual symptom among Heidenhain cases. Heidenhain phenotype can occur in genetic CJD cases. PRNP mutation status might be an important prognostic factor for Heidenhain cases.

Teaching Video NeuroImages: Optic Ataxia as the Presenting Sign of the Heidenhain Variant of Creutzfeldt-Jakob Disease.

A 59-year-old woman presented with subacute onset of hand clumsiness followed by memory loss. She reported difficulty reaching for objects, although she could see them. Examination (video) showed optic ataxia, visual acuity of 20/30 OU, intact visual field, and near-normal finger-to-nose test. Hyperintense signals in the left temporo-parieto-occipital cortex in diffusion-weighted MRI, periodic triphasic complexes in EEG (figure), and elevated t-tau in CSF suggested the Heidenhain variant of Creutzfeldt-Jakob disease.1 The patient received supportive care and progressed to akinetic mutism. Optic ataxia—inaccuracy of visually guided arm movements—is a visuomotor disorder associated with lesions involving the posterior parietal cortex.2

Heidenhain Variant of Creutzfeldt-Jakob Disease with Concurrent Findings of Posterior Reversible Encephalopathy Syndrome: A Case Report and Literature Review

Although Creutzfeldt-Jakob disease is not yet proved to be related to the development of posterior reversible encephalopathy syndrome, prion invasion to the endothelium has been shown to change blood-brain barrier permeability. We present a case of Heidenhain variant of Creutzfeldt-Jakob disease that had associated imaging findings of posterior reversible encephalopathy syndrome, with a review of the literature, raising the question of whether Creutzfeldt-Jakob disease instead represents another cause for the development of posterior reversible encephalopathy syndrome.

HEIDENHAIN VARIANT OF CREUTZFELDT-JAKOB DISEASE IN BRAZIL: A CASE REPORT

Creutzfeldt-Jakob disease (CJD) is a rare spongiform encephalopathy characterized by a rapid neurodegenerative progress, caused by a misfolded variant of the cellular prion protein (PrP) known as PrPSc. The clinical presentation of sCJD includes a wide range of neurological signs of cortical, subcortical, or cerebellar origin, either isolated or in various combinations. Due to this protean clinical presentation form, sCJD must be distinguished from other dementias. In this case report, we discuss the Heidenhain variant of Creutzfeldt-Jakob disease (HvCJD), a rare variant characterized by early visual symptoms and typical findings in imaging scans. Our patient presented rapidly progressive dementia and a history of visual hallucinations. As for other prion diseases, only symptomatic treatment is available for HvCJD. Thirty years of clinical investigation of patients with prion disease have resulted in little progress in either defining or evaluating potential treatments.

Differential diagnosis of isolated visual disturbances, management of prion diseases and the heidenhain variant of Creutzfeldt-Jakob disease

Differential diagnosis of isolated visual disturbances, management of prion diseases and the heidenhain variant of Creutzfeldt-Jakob disease

The dark side of the (half) moon

A 71-year-old man was referred to neuro-ophthalmology for evaluation of reading problems associated with pituitary adenoma. Perimetry showed a right temporal crescent syndrome (“half moon” syndrome) suggesting left occipital disease. Cranial magnetic resonance imaging, electroencephalogram, and cerebrospinal fluid examination (14-3-3 protein) were consistent with a diagnosis of Creutzfeldt-Jakob disease. His neurologic condition rapidly deteriorated with memory problems, myoclonus, and apathy followed by death, 4 months later. This case shows how visual problems may be the first manifestation of this rare prion disease (Heidenhain variant of Creutzfeldt-Jakob disease).

Diagnostic challenge of non‐specific visual symptoms: consideration of Heidenhain variant of Creutzfeldt‐Jakob disease

Diagnostic challenge of non‐specific visual symptoms: consideration of Heidenhain variant of Creutzfeldt‐Jakob disease

P 164 Parietal stroke mimicking the Heidenhain variant of Creutzfeldt-Jakob Disease

The Heidenhain variant of Creutzfeldt-Jakob disease (CJD) is a rapidly progressive neurodegenerative disease with an occipito-parietal focus.It initially presents with visual disturbances such as visual agnosia or cortical blindness (Kropp et al., 1999).After presentation of early visual symptoms, rapid progression of dementia and death follows.While the Heidenhain variant matches neuropathological criteria of CJD, differential diagnosis from other neurological disorders using biomarkers from electroencephalography (EEG), magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) reveal low sensitivity and specificity.As a consequence, these tools may lead to an erroneous diagnosis of the Heidenhain variant. We report about a 81-year old female who was transferred to the intensive care unit due to a generalized tonic-clonic seizure followed by prolonged somnolence, additionally exhibiting myoclonic jerks of the distal legs, left horizontal gaze palsy and horizontal nystagmus to the right.A history of cognitive decline including short-term memory and word-finding difficulties as well as visuospatial and visuoconstructive deficits over the last few weeks was reported. Initial EEG revealed 1.5 Hz left lateralized periodic sharp-wave and polyspike-wave complexes of high amplitude and triphasic morphology suspicious for CJD. Brain MRI showed a hyperintense lesion in the left occipito-parietal lobe on diffusion-weighted and FLAIR sequences, respectively.Protein 14-3-3 was positive in CSF (ELISA). However, RT-QuIC confirmatory test was negative.Other serum and CSF parameters including anti-neuronal antibodies were negative.Given this information, is it reasonable to consider the Heidenhain variant of CJD? The patient suffered from a cardioembolic stroke due to atrial fibrillation affecting the parietal branches of the middle cerebral artery.Edoxaban had been removed three weeks previously because of repeated falls.During ICU treatment, the patient developed a prolonged nonconvulsive status epilepticus (NCSE) characterized by deep coma without significant motor phenomena.EEG was refractory to an initial antiepileptic drug treatment, but finally returned to normal with valproate monotherapy.The patient, however, remained comatose until transfer to rehabilitation, but she regained consciousness two weeks later. This case points out that a parietal stroke with complicating NCSE may mimic the Heidenhain variant of CJD, particularly by under-recognition of so-called CJD red flags: First, the occurrence of 14-3-3 proteins is known to be positive after either acute stroke or seizures.Secondly, though increased intensity on DWI in CJD is discussed as a noninvasive biomarker, such signal abnormalities – particularly if sparing the basal ganglia – are not specific to CJD. Thirdly, NCSE patients with altered consciousness often present with localized or lateralized sharp waves of triphasic configuration.These atypical triphasic waves are considered to be of epileptic origin if they disappear following antiepileptic drug treatment as in our case (Trinka and Leitinger, 2015).

Of grave concern

A 73-year-old woman presented with vision loss and recurrent proptosis with conjunctival chemosis 4 weeks after an uncomplicated fat-only orbital decompression for thyroid eye disease. Her Graves disease was biochemically “burnt out,” and she had diabetes mellitus. Initial neuro-imaging showed a straightened optic nerve and orbital apex fat streaking so a bilateral bony decompression of the orbital apex was performed for presumed compressive optic neuropathy. Vision failed to improve, and she experienced cognitive decline. She described metamorphopsia and insomnia. Examination showed a hemifield loss of red sensitivity, difficulties with higher visual processing, and memory problems. Occipital cortical ribboning was seen on diffusion weighted magnetic resonance imaging, cerebrospinal fluid was positive for 14-3-3, and her electroencephalogram showed periodic complexes. A diagnosis of the Heidenhain variant of Creutzfeldt-Jakob disease was made. She became akinetic and mute, dying a few months later.

Imaging and EEG findings of Rare Heidenhain Variant of Creutzfeldt-Jakob Disease

Background: Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative spongiform encephalopathy. Findings are usually consistent with basal ganglia and frontal lobe destruction. However in certain variants, the clinical and diagnostic findings can differ. This case illustrates the occipital findings of the rare Heidenhain variant of CJD. Methods: We describe the clinical course and radiologic findings of a 65-year-old with the Heidenhain variant of Creutzfeldt-Jakob disease. Diagnostic studies included lumbar puncture, EEG and MRI scans of the brain. Results: This case illustrates the findings of the rare Heidenhain variant of CJD, including prominent changes in MRI and EEG in the occipital region. This was further supported by the positive enolase and 14-3-3 in cerebral spinal fluid. Conclusions: In patients presenting with clinical symptoms of visual disorders of unclear origin presenting with or shortly after psychosis or dementia, this variant of CJD must be considered in the differential diagnosis.

Visual symptoms in the presentation of Creutzfeldt–Jakob disease

We describe a 68-year-old man with a previous history of neurosurgical repair of a skull fracture, who presented to the ophthalmology clinic with progressive visual decline. His initial visual acuity was 6/30 in the right eye and 6/48 in the left, and over 2weeks this progressed to hand movements in both eyes. No ocular abnormalities were identified. He was noted to be increasingly confused and a subsequent MRI showed extensive bilateral posterior cortical changes consistent with cytotoxic oedema. An electroencephalogram was suggestive of encephalopathy, particularly involving the occipital lobe. He was diagnosed with the Heidenhain variant of Creutzfeldt–Jakob disease (CJD), confirmed by a positive cerebrospinal fluid 14-3-3 protein. Classically, patients with CJD present with rapidly progressive cognitive decline, ataxia and myoclonus. However, visual symptoms are a common and perhaps underrecognised manifestation of CJD. Patients can present with isolated visual symptoms which precede cognitive decline by weeks due to predominantly occipital lobe disease. This presentation is classified as the Heidenhain variant of CJD.

The Heidenhain variant of Creutzfeldt-Jakob disease – two patients initially misdiagnosed with dissociative disorder

Summary Background: The Heidenhain variant of sporadic Creutzfeldt-Jakob disease is characterized by prominent visual complaints that last in isolation for some weeks and are often misdiagnosed until rapid cognitive decline with suggestive neurological symptoms appear. The treatment is only symptomatic, but correct diagnosis established at the time of visual symptom isolation helps to avoid needless diagnostic or treatment procedures and may give time to patients and their families to prepare for the worst. Case Report: We report on 2 cases based on available medical documentation. Written informed consents for publication were obtained from the patients’ families after the patients’ deaths. We report on the cases of 2 men with sporadic Creutzfeldt-Jakob disease first manifested with visual symptoms in which ophthalmological and neurological background was excluded and misdiagnoses of dissociative disorder were made. Further diagnosis in a psychiatry ward suggested probable sporadic Creutzfeldt-Jakob disease, which was confirmed at postmortem examination. Conclusions: Although visual symptoms are listed in the World Health Organization diagnostic criteria for sporadic Creutzfeldt-Jakob disease, initial symptoms can be vague enough to be misdiagnosed even by neurologists. We conclude that in visual disturbances in which ophthalmological and neurological background is at first excluded, a differential diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) should be considered. In patients with a diagnosis of visual dissociative disturbances, the Heidenhain variant of sCJD should be considered in the differential diagnosis. Repeated EEG in patients with visual disturbances of unknown cause can detect abnormalities suggestive of sporadic Creutzfeldt-Jakob disease.

Heidenhain variant of Creutzfeldt-Jakob disease: An autopsy study from India.

Prion diseases are rare, progressive and fatal neurodegenerative diseases characterized by long incubation period and short clinical course. We present a rare case of Heidenhain variant of Creutzfeldt-Jakob disease, occurring in a 55-year-old lady presenting with dementia, cortical blindness, and myoclonic jerks. She succumbed to the disease within 8 weeks of onset of symptoms. MRI revealed hyperintense signals on T2WI and fluid attenuated inversion recovery (FLAIR) images in basal ganglia and fronto-temporal and parietal cortex, sparing thalamus, striate cortex and globus pallidum. Abundant abnormal prion protein deposits (PrPsc) were detected in caudate, putamen, thalamus, cingulate and striate cortex, in comparison to frontal and parietal cortex while no deposits were found in globus pallidum. MRI changes did not correlate with degree of spongy change, gliosis or prion protein deposition. The cause for abnormal signal changes in MRI and FLAIR images remains unclear.

A Case of Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease

Purpose: To report a case of the Heidenhain variant of sporadic Creutzfeldt-Jakob disease (CJD), predominantly characterized by visual impairment at onset. Case summary: History-taking, ophthalmologic examination, neurologic examination, cerebrospinal fluid examination including 14-3-3 protein analysis, and brain MRI were performed in a 48-year-old man with progressive visual loss and a visual field defect. These symptoms were accompanied by visual illusion and macropsia. Neurologic examination revealed relatively rapidly progressing cognitive impairment, ataxia, aphasia, and myoclonus. The 14-3-3 protein was detectable in otherwise normal CSF samples. The diffusion weighted brain MRI showed increased signal intensity in both occipital lobes, the basal ganglia, the temporal and frontal lobes. He was clinically diagnosed as having a Heidenhain variant of sporadic CJD. Conclusions: In a patient with a rapidly progressive visual loss, visual field defects, visual illusion, and neurologic abnormalities including progressive dementia, ataxia, aphasia, and myoclonus, the Heidenhain variant of CJD should be considered. Because prions, a cause of CJD, exhibit unusual resistance to conventional chemical and physical decontamination methods, it is necessary to have an appropriate management scheme to prevent the spread of infection.

A Case of Orbital Malignant Lymphoma associated with Acquired Immunodeficiency Syndrome (AIDS)

Purpose: To report a case of the Heidenhain variant of sporadic Creutzfeldt-Jakob disease (CJD), predominantly characterized by visual impairment at onset. Case summary: History-taking, ophthalmologic examination, neurologic examination, cerebrospinal fluid examination including 14-3-3 protein analysis, and brain MRI were performed in a 48-year-old man with progressive visual loss and a visual field defect. These symptoms were accompanied by visual illusion and macropsia. Neurologic examination revealed relatively rapidly progressing cognitive impairment, ataxia, aphasia, and myoclonus. The 14-3-3 protein was detectable in otherwise normal CSF samples. The diffusion weighted brain MRI showed increased signal intensity in both occipital lobes, the basal ganglia, the temporal and frontal lobes. He was clinically diagnosed as having a Heidenhain variant of sporadic CJD. Conclusions: In a patient with a rapidly progressive visual loss, visual field defects, visual illusion, and neurologic abnormalities including progressive dementia, ataxia, aphasia, and myoclonus, the Heidenhain variant of CJD should be considered. Because prions, a cause of CJD, exhibit unusual resistance to conventional chemical and physical decontamination methods, it is necessary to have an appropriate management scheme to prevent the spread of infection.

Multitracer PET imaging in a patient with Heidenhain variant of Creutzfeldt-Jakob disease

Multitracer PET imaging in a patient with Heidenhain variant of Creutzfeldt-Jakob disease

The Heidenhain variant of Creutzfeldt-Jakob disease.

To investigate whether typical neuropathological and radiological findings can be identified in patients with the clinical diagnosis of the Heidenhain variant of Creutzfeldt-Jakob disease (CJD). Case study. The clinical symptoms, neuropathological findings, electroencephalograms, magnetic resonance images, and cerebrospinal fluid samples of 14 Heidenhain cases were evaluated. Neuropathological changes were compared with those in a group of 14 patients with ataxia as the leading clinical sign. A university hospital, base of the German National Creutzfeldt-Jakob Disease Surveillance Study. Medical records of 169 neurologically examined patients with prospectively classified and neuropathologically confirmed CJD were analyzed. Difference in neuropathological and radiological findings between patients with the Heidenhain variant and other patients with CJD. Of 169 patients with confirmed CJD, 20% showed characteristic clinical findings such as blurred vision, visual field restriction, metamorphopsia, or cortical blindness. Disease course of the Heidenhain group, as compared with the group of all patients with definite CJD, was significantly shorter (5.7 months vs 7.5 months; P=.02, t test). Neuropathological examination of patients with the Heidenhain variant showed most pronounced changes in the occipital lobe but less damage in the cingulate gyrus and basal ganglia compared with 14 patients with CJD who had ataxia as the leading clinical sign. Eleven (92%) of 12 genetically analyzed Heidenhain cases were homozygous for methionine at codon 129 of the prion protein gene (PRNP). In 9 of 9 cases, the 14-3-3 protein was present. In 7 (78%) of 9 cases, the level of neuron-specific enolase was elevated, with a concentration above 35 ng/mL. Periodic sharp-wave complexes were observed in 11 (78%) of the 14 cases. In 7 (63%) of 11 patients, magnetic resonance images showed symmetric hyperintensities in the basal ganglia in the T2- and proton-weighted sequence. In 4 of 11 cases the T2- and proton density-weighted images showed a pronounced signal increase confined to the gray matter of the occipital and visual cortex. Isolated atrophy of the visual cortex was noticeable in 2 of 11 cases. The clinical presentation of the Heidenhain variant of CJD was shown to correlate with the neuropathological findings of gliosis and nerve cell loss. In patients with visual disorders of unclear origin and signs of dementia, the differential diagnosis of a Heidenhain variant of CJD must be taken into consideration.