Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease with a Variety of Visual Symptoms: A Case Report with Autopsy Study.

BACKGROUND Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal disease caused by the change of prion protein (PrP). Affected patients present with rapidly progressive cognitive dysfunction, myoclonus, or akinetic mutism. Diagnosing the Heidenhain variant of sCJD, which initially causes various visual symptoms, can be particularly difficult. CASE REPORT A 72-year-old woman presented with a 2- to 3-month history of photophobia, blurring vision in both eyes. Seven days previously, she showed visual impairment of 20/2000 in both eyes. Left homonymous hemianopia and restricted downward movement of the left eye were observed with an intact pupillary light reflex and normal fundoscopy. On admission, her visual acuity was light perception. Cranial magnetic resonance imaging revealed no abnormality, and electroencephalography showed no periodic synchronous discharges. Cerebrospinal fluid examination on the sixth hospital day revealed tau and 14-3-3 protein with a positive result of real-time quaking-induced conversion. She thereafter developed myoclonus and akinetic mutism and died. Autopsy revealed thinning and spongiform change of the cerebral cortex of the right occipital lobe. Immunostaining showed synaptic-type deposits of abnormal PrP and hypertrophic astrocytes. Consequently, she was diagnosed with the Heidenhain variant of sCJD with both methionine/methionine type 1 and type 2 cortical form based on the western blot of cerebral tissue and PrP gene codon 129 polymorphism. CONCLUSIONS When a patient presents with various progressive visual symptoms, even without typical findings of electroencephalography or cranial magnetic resonance imaging, it is essential to suspect the Heidenhain variant of sCJD and perform appropriate cerebrospinal fluid tests.

On the pathophysiology and treatment of akinetic mutism.

Akinetic mutism (AM) is a rare neurological disorder characterized by the presence of an intact level of consciousness and sensorimotor capacity, but with a simultaneous decrease in goal-directed behavior and emotions. Patients are in a wakeful state of profound apathy, seemingly indifferent to pain, thirst, or hunger. It represents the far end within the spectrum of disorders of diminished motivation. In recent years, more has become known about the functional roles of neurocircuits and neurotransmitters associated with human motivational behavior. More specific, there is an increasing body of behavioral evidence that links specific damage of functional frontal-subcortical organization to the occurrence of distinct neurological deficits. In this review, we combine evidence from lesion studies and neurophysiological evidence in animals, imaging studies in humans, and clinical investigations in patients with AM to form an integrative theory of its pathophysiology. Moreover, the specific pharmacological interventions that have been used to treat AM and their rationales are reviewed, providing a comprehensive overview for use in clinical practice.

Acute inferior homonymous quandrantanopia in a 71-year-old woman.

A 71-year-old woman presented with acute inferior homonymous quadrantanopia initially mimicking acute ischemic stroke. As clinical signs and symptoms progressed to akinetic mutism with myoclonus the diagnosis of the Heidenhain variant of Creutzfeldt-Jakob disease was made. Brain MRI 4 days after symptom onset revealed ribbon-like high signal intensity in the medial occipital cortex.

[White matter abnormalities following attempted suicide]. / Wittestofafwijkingen na een zelfmoordpoging.

BACKGROUND: Delayed post-hypoxic leukoencephalopathy (DPHL) is a demyelinating disorder characterized by neuropsychiatric symptoms occurring a few days to some weeks following cerebral hypoxia. CASE DESCRIPTION: A 50-year old female patient showed rapidly progressive cognitive deterioration with apathy, mutism and regressive behaviour a few weeks after a suicide attempt with carbon monoxide (CO). This eventually leads to a state of akinetic mutism. Magnetic resonance imaging (MRI) of the brain showed diffuse white matter abnormalities. These MRI findings combined with CO intoxication and the clinical picture were highly suggestive for DPHL. CONCLUSION: This case emphasizes that a neurological cause should be considered if rapidly progressive neuropsychiatric symptoms occur, and that after suspected auto intoxication it is important to take possible hypoxia and its after-effects into consideration. Recognition of DPHL is important so that unnecessary invasive diagnostics and treatment can be avoided. Considering the favorable natural course of DPHL appropriate measures should be taken in order to provide supportive care and rehabilitation.

Motivation of extended behaviors by anterior cingulate cortex.

Intense research interest over the past decade has yielded diverse and often discrepant theories about the function of anterior cingulate cortex (ACC). In particular, a dichotomy has emerged between neuropsychological theories suggesting a primary role for ACC in motivating or 'energizing' behavior, and neuroimaging-inspired theories emphasizing its contribution to cognitive control and reinforcement learning. To reconcile these views, we propose that ACC supports the selection and maintenance of 'options' - extended, context-specific sequences of behavior directed toward particular goals - that are learned through a process of hierarchical reinforcement learning. This theory accounts for ACC activity in relation to learning and control while simultaneously explaining the effects of ACC damage as disrupting the motivational context supporting the production of goal-directed action sequences.

Reversible acute encephalopathy with mutism, induced by calcineurin inhibitors after renal transplantation.

The incidence of neurotoxicity from calcineurin inhibitors varies by the organ transplanted. Akinetic mutism is characterized by the inability to perform voluntary movements and express language, without alterations in mental status. This process has been reported in neurotoxicity due to high serum levels of calcineurin inhibitors, but in rare cases, it presents as a form of tacrolimus toxicity after renal transplantation, despite normal serum levels. We report a clinical case of a renal transplant patient in whom reversible acute encephalopathy and akinetic mutism developed. Brain lesions appeared on magnetic resonance imaging, and the condition resolved after the drug was withdrawn.

Serial diffusion-weighted MRI and SPECT findings in a Creutzfeldt-Jakob disease patient with V180I mutation.

We report serial changes of diffusion-weighted imaging (DWI) and single photon emission computed tomography (SPECT) in a patient with Creutzfeldt-Jakob disease with V180I mutation (CJD180). DWI abnormalities in our patient were more predominantly observed in the left cerebral cortex than left basal ganglia. Hemilateral abnormalities progressed over 5 months to involve the contralateral side with increasing DWI signals. At 6 months, SPECT showed hypoperfusion in the left parietal and frontal lobes and the hypoperfusion region spread to the bilateral basal ganglia, right parietal and frontal lobes. SPECT imaging revealed marked cerebral blood flow reduction, predominantly in the cerebral cortex corresponding to brain areas with high-intensity DWI signals. During the follow-up period of CJD180, DWI was more sensitive than conventional FLAIR and T2-weighted images (T2WI) to detect and monitor the progression of abnormal hyperintense lesions. We suggest that serial DWI and SPECT findings are useful for not only early diagnosis of CJD but also for monitoring disease progression.

Thalamic infarct presenting as catastrophic life-threatening event in an older adult.

An 84 year old woman with history of moderate Alzheimer's disease, depression, and an anxiety disorder presented to our emergency room at Victoria Hospital, London, Ontario in an 'unresponsive' state. The patient was akinetic with mutism, and clonic perseveration induced in the upper limbs was evident while she was examined. Heart attack, massive stroke, or intracranial bleed were ruled out, and an electroencephalogram showed no epileptiform activity. Despite a normal CT, a magnetic resonance scan was ordered and showed bilateral acute paramedian thalamogeniculate infarction arising from occlusion of the artery of Percheron. Bilateral thalamic infarcts can cause sudden onset of akinetic mutism with clonic perseveration, which may be confused with coma and seizures due to life threatening conditions such as a massive stroke. Thorough clinical assessment and early use of MRI scanning will assist physicians with a more accurate diagnosis of older adults with this kind of presentation.

[Creutzfeldt - Jakob presenting with isolated visual symptoms: the Heidenhain variant]. / Creutzfeldt - Jakob con debut oftalmológico: la variante Heidenhain.

CLINICAL CASE: We report the case of a 67 year old female complaining of decreased vision and diagnosed with the Heidenhain variant of sporadic Creutzfeldt-Jakob disease. Her past medical history was unremarkable. She died less than three months after the onset. DISCUSSION: The Heidenhain variant of sporadic Creutfeld-Jakob disease should be suspected in patients suffering from early visual disturbances, unremarkable ophthalmic examination, and subsequent rapid decline of their cognitive function. A complete neurological exam including electroencephalogram recordings and magnetic resonance is mandatory. These patients share a common genotype (PRNP codon 129 MM) associated with a clinically typical disease course.

Akinetic mutism--not coma.

We describe a case of akinetic mutism mistaken as coma. A 77-year old lady presented with apparent unresponsiveness. In fact she responded when stimulated. She subsequently developed movements typical of clonic perseveration, erroneously treated as seizures. She also had features of a frontal lobe syndrome. Initial CT scan showed no abnormality; it was only after an MRI scan that a diagnosis of bilateral paramedian thalamic infarction was made. MRI scanning should be considered early in the investigation of patients with atypical neurological presentation.

Relationship between clinical course and Diffusion-weighted MRI findings in sporadic Creutzfeldt-Jakob Disease.

The aim of this study was to investigate the relationship between clinical course and diffusion-weighted MRI (DWI) findings in sporadic Creutzfeldt-Jakob Disease (sCJD). We reviewed clinical records and MRI examination in nine probable sCJD. According to hyperintense signal distribution on DWI, the patients were classified into two groups with cortical ribbon plus basal ganglia hyperintensity (6/9) and with only increased cortical signals (3/9). Clinical features including quadriparesis (3/6), akinetic mutism (2/6), and dysphasia (2/6), which were usually observed in the more advanced stage of CJD, were noted only in patients with cortical ribbon plus basal ganglia hyperintensity at the time of initial DWI examination. The patients with the cortical plus basal ganglia hyperintensity (6.4+/-1.7 weeks) had a shorter interval from symptom onset to akinetic mutism than those with only cortical ribbon hyperintensity (26.0+/-22.5 weeks) (p=0.02). These findings suggest that DWI may predict the clinical course of CJD.

Inflammatory cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Sporadic Creutzfeldt-Jakob disease (CJD) is a fatal, transmissible spongiform encephalopathy characterized by rapidly progressive dementia, myoclonus, ataxia and akinetic mutism. The underlying mechanism is believed to be a conformational change of a native prion protein which characteristically fails to provoke an immune response. Commensurate with the latter, cerebrospinal fluid (CSF) classically exhibits a non-inflammatory profile. CASES: We report two patients with pathologically-proven sporadic CJD presenting with a significant CSF pleocytosis. CONCLUSION: Although uncommon, the presence of an inflammatory CSF profile should not exclude the diagnosis of sporadic CJD.

Chronological changes in MRI and CSF biochemical markers in Creutzfeldt-Jakob disease patients.

BACKGROUND: There are currently no markers for evaluating chronological changes in Creutzfeldt-Jakob disease (CJD). We examined if chronological changes in biochemical markers in cerebrospinal fluid (CSF) and diffusion-weighted magnetic resonance imaging (DWI) were utilizable for this purpose. METHODS: Ten independent patients were divided into two groups of 5 patients each. We analyzed CSF biochemical markers, DWI and the clinical course in one group. In the remaining group, only the CSF biochemical markers were analyzed before and after the onset of akinetic mutism. RESULTS: The level of total tau (t-tau) protein in CSF in the early phase after disease onset was 2,655 +/- 423.9 pg/ml, reaching a mean peak of 14,675 +/- 1,240 pg/ml in the middle phase and gradually declining after that. Just before patients deteriorated into akinetic mutism, t-tau protein titers reached a maximum (8,786 +/- 2,975 pg/ml). There were dramatic changes in t-tau protein levels throughout the clinical course, unlike the other markers. DWI was not always utilizable, because of discordance with clinical symptoms seen in this study. Four cases exhibited peaks in t-tau protein levels while the patients fell into akinetic mutism except 1 case. CONCLUSION: Our results suggest that t-tau protein is the most sensitive marker of disease progression in CJD patients.

Bithalamic lesions of butane encephalopathy.

Butane inhalation can cause serious medical complications and is particularly toxic to the nervous system. This is a report of an acutely encephalopathic youth with prominent abulia. MRI revealed severe bithalamic injury attributed to butane toxicity. Clinical issues, including particular radiologic findings, related to butane inhalation are reviewed.

Consciousness and altered consciousness.

The notion of consciousness in the English scientific literature denotes a global ability to consciously perform elementary and intellectual tasks, to reason, plan, judge and retrieve information as well as the awareness of these functions belonging to the self, that is, being self-aware. consciousness can also be defined as continuous awareness of the external and internal environment, of the past and the present. The meaning of consciousness is different in various languages, but it invariably includes, the conscious person is capable to learn, retrieve and use information. Disturbance or loss of consciousness in the Hungarian medical language indicates decreased alertness or arousability rather than the impairment of the complex mental ability. Awareness denotes the spiritual process of perception and analysis of stimuli from the inner and external world. Alertness is a prerequisite of awareness. Clinical observations suggest that the lesions of specific structures of the brain may lead to specific malfunction of consciousness, therefore, consciousness must be the product of neural activity. "Higher functions" of human mental ability have been ascribed to the prefrontal and parietal association cortices. The paleocerebrum, limbic system and their connections have been considered to be the center of emotions, feelings, attention, motivation and autonomic functions. Recent evidence indicates that these phylogenetically ancient structures play an important role in the processes of acquiring, storing and retrieving information. The hippocampus has a key role in regulating memory, learning, emotion and motivation. Impaired consciousness in the neurological practice is classified based on tests for conscious behavior and by analyzing the following responses: 1. elementary reactions to sensory stimuli--these are impaired in hypnoid unconsciousness, 2. intellectual reactions to cognitive stimuli--these indicate the impairment of cognitive contents in non-hypnoid unconsciousness. Obviously, disturbance of elementary reactions related to alertness and disturbance of intellectual performance overlap. In conditions with reduced ability to react to or to perceive external stimuli the cognitive disturbance of consciousness cannot fully be explored.

Akinetic mutism following stroke.

This is an appraisal of the varied clinical presentation and the neural substrate for akinetic mutism following stroke. The diagnosis is important as akinetic mutism is often misdiagnosed as depression, delirium and locked-in-syndrome. This is a descriptive study of eight selected patients with akinetic mutism following infarction/haemorrhage in different regions of the brain with characteristic syndromes. They involved the critical areas namely, the frontal (cingulate gyrus, supplementary motor area and dorso-lateral border zone), basal ganglia (caudate, putamen), the mesencephalon and thalamus. The disorders of speech and communication took different forms. The speech disorder included verbal inertia, hypophonia, perseveration, softened and at times slurred. The linguistic disturbances were fluent, non-fluent, anomia and transcortical (motor, mixed) aphasias. The findings were related to what is known about the neuroanatomic location of the lesions and the role of the frontal-subcortical circuitry in relation to behaviour. Akinetic mutism could be explained by damage to the frontal lobe and or interruption of the complex frontal subcortical circuits.