168Chapter 10: Over-reliance on negative test results

Homonymous hemianopia with negative neuro-imaging

Case: A 60-year-old farmer developed progressive difficulty seeing to the left. This was initially an isolated symptom, with no other focal deficits, alteration of mental status or systemic symptoms. Two weeks later he developed, in addition, some clumsiness and mild confusion. Ophthalmic examination four weeks after onset showed a fairly dense left homonymous hemianopia with otherwise normal findings. A stroke or tumor of the right occipital lobe was suspected, but an MR scan was normal.

What disease processes would you consider here?

The list of diseases that can produce focal occipital dysfunction without accompanying MRI changes is a short one: non-ketotic hyperglycemia, Alzheimer’s disease, Creutzfeldt–Jakob disease, complicated migraine, hypoxic-ischemic encephalopathy and occipital seizures (ictal or post-ictal). This patient’s blood glucose and electrolytes were normal and he had no personal or family history of migraine. His course was thought to be too rapid for Alzheimer’s disease. A lumbar puncture was positive for the 14-3-3 protein and he received a diagnosis of Creutzfeldt–Jakob disease. He was given supportive care and over the next several weeks he exhibited further cognitive decline with new onset of frequent myoclonic jerks. He passed away at home eight weeks after onset of his symptoms.

Discussion: Creutzfeldt–Jakob disease (CJD) is one of several spongiform encephalopathies caused by a transmissible pathogenic form of the prion protein, a normal constituent of cell membranes. Prion diseases affect animals and humans, have a long incubation period before onset of neurologic deterioration and are invariably fatal. In animals, the pathogenic prion is transmitted during direct contact with an infected animal or by consumption of infected feed. Animal prion diseases include scrapie, bovine spongiform encephalopathy (so-

called “mad cow disease”) and transmissible mink encephalopathy.

Human prion disease can be divided into familial forms (familial CJD, Gerstmann–Straussler– Scheinker disease and fatal familial insomnia), nonfamilial CJD (sporadic, variant and iatrogenic types) and kuru. Only 10–15% of cases in humans are familial. In the majority of human cases the mode of transmission is unknown. Occasional cases result from iatrogenic infection, occurring in recipients of dural grafts, corneal transplants and growth hormone extract from cadaver pituitary glands. In a remote region of New Guinea, a prion disease known as kuru was found to be transmitted by the ancient practice of ritual cannibalism during bereavement ceremonies. Once reaching epidemic proportions several decades ago, kuru has nearly disappeared since the suppression of cannibalism. In the mid 1990s a clustering of cases in Great Britain was linked to an outbreak of bovine spongiform encephalopathy, although the exact route of transmission was unclear. These patients were clinically and histopathologically distinct from the more common sporadic form of CJD. Termed variant CJD (vCJD), these patients were younger (mean age 29 years), had a more protracted period of psychiatric symptoms before onset of dementia and death, and did not show the typical electroencephalography (EEG) and MRI changes of sporadic CJD.

Sporadic CJD is the most common form of human prion disease. It has no geographic or gender preference and the average age at onset is 60 years. Its mode of transmission is unknown. Neurologic manifestations of sporadic CJD are varied, most commonly taking the form of rapidly progressive dementia with myoclonic jerks. In some patients, the disease presents primarily as a progressive cerebellar syndrome; in others amyotrophy is prominent. In one particular form, the brunt of the disease process affects the posterior cerebral hemispheres, causing homonymous defects, cortical blindness and a variety of higher cortical visual deficits. This form is referred to as the Heidenhain variant and, for reasons that are unclear, it has a more rapidly