The woman who did not recognise her own face

Discussion

This case history is an example of the extensive variation that can be seen in the presentation of cerebral venous thrombosis (CVT). This condition encompasses thrombosis in cerebral veins and dural sinuses, and in the latter case it is often referred to as cerebral venous sinus thrombosis.

CVT is rare but probably underdiagnosed, with an estimated incidence of less than 1 in 100 000 population per year. Less than 1 % of all cases of stroke are due to CVT complicated by haemorrhagic infarction (4). Pathophysiological mechanisms in all venous thrombus formation can be explained on the basis of Virchow’s triad: factors relating to the vascular endothelium, haemodynamics and/or coagulability of the blood itself (5). Key risk factors for thrombosis are infections, congenital thrombophilia, and hypercoagulopathy as seen in conditions such as malignancy and systemic rheumatic diseases. In the general population, venous thrombosis occurs most frequently in persons under the age of 40 and is more common in women than in men, probably due to oestrogen-containing oral contraceptives and pregnancy (4).

Our patient did not have congenital thrombophilia, and screening with chest X-ray, mammography and gynaecological examination raised no suspicion of malignancy (6). The patient was using the hormonal coil intrauterine system (non-oestrogen-based), in addition to daily adrenergic and corticosteroid inhalers (salmeterol-fluticasone) and prednisolone cures to treat asthma exacerbations.

A Danish registry-based case-control study described a dose-dependent increase in the risk of venous thromboembolism in the lower extremities and lungs following glucocorticoid therapy (7). The risk was greatest with systemic use but was also found to be increased with other routes of administration, including inhalation. Patients with venous thrombosis in other locations were not included in the study, but glucocorticoid use has been listed elsewhere as a risk factor for CVT (8). Thus, a possible connection between our patient’s steroid use and CVT cannot be ruled out.

D-dimer has a diagnostic sensitivity of 94 % and specificity of 90 % for CVT. Our patient had a false-negative D-dimer test. False negative D-dimer is most often seen in association with isolated headache, prolonged symptoms and limited sinus involvement (9). Imaging is therefore recommended upon clinical suspicion of CVT, with cerebral MRI with venous angiography as the gold standard (4).

The most frequently reported symptom of CVT is headache, which is present in up to 90 % of cases and in 9 % is the only symptom. More than half of patients have a subacute onset with headache that increases in inensity over a few days. One third of cases have an acute onset over the course of 24 hours, whereas only a minority have a chronic course. In addition to headache, elevated intracranial pressure may cause vomiting, papilloedema and visual disturbances. CVT may also cause a focal syndrome, with focal neurological deficits and seizures, or an encephalopathy syndrome, with bilateral or multifocal signs and possible disturbances of consciousness (8).

Our patient had clear cognitive symptoms that suggested involvement of one particular area of the brain. The most striking finding was her inability to recognise faces and familiar surroundings. Deficits in the brain’s ability to interpret visual stimuli can be divided into those that reflect disruption to the association fibres projecting from the occipital lobe to the parietal lobe («where» pathway deficits) and those that reflect disruption to the association fibres projecting to the temporal lobe («what» pathway deficits) (Fig. 2) (10, 11). The visual agnosias belong to the latter group. They are usually defined as an inability to recognise objects that is not due to sensory impairment or general intellectual impairment (i.e., «what» pathway deficits).

Prosopagnosia (from the Greek «prosopon» for face and «gnosis» for knowledge) is a specific visual agnosia in which affected individuals are unable to recognise a familiar face from looking at the person or an image, even though they correctly identify the object as a face and can point out distinguishing features such as glasses, facial hair or voice (12). The neurologist and author Oliver Sacks described a patient with prosopagnosia in his essay «The man who mistook his wife for a hat». While visiting the patient at home, Sacks commented on the pictures of different people hanging on the wall: «By and large, he recognised nobody: neither his family, nor his colleagues, nor his pupils, nor himself. He recognised a portrait of Einstein because he picked up the characteristic hair and moustache.» (13).

A small number of cases that have been examined anatomically and with CT or MRI scans indicate that prosopagnosia is usually associated with bilateral medial occipitotemporal lesions. There are also rare cases caused by unilateral injury, almost always on the right side (14). Our patient’s thrombus was in fact in the right transverse sinus (Fig. 1). Venous drainage from the temporal lobe into the transverse sinus occurs via the vein of Labbé (inferior anastomotic vein), and venous stasis here can cause circulatory disturbances in associated brain tissue. MRI revealed no diffusion abnormalities or other parenchymal changes. However, no signal was detected in the vein of Labbé on the side in question, whereas a good signal was obtained in the contralateral vein (Fig. 3). On balance, we consider it likely that the MRI findings are related to the patient’s cognitive symptoms.

Human studies using techniques such as functional MRI (fMRI) have provided strong evidence for the existence of a small area within the fusiform gyrus of the temporal lobe where most of the neurons are face-specific (Fig. 4) (15). The idea of a «face area» in the fusiform gyrus is an oversimplification, but one which is conveyed uncritically in popular culture and which turned up in the James Bond film «Spectre» during the patient’s convalescence. In a scene in which Bond is strapped to a chair loaded with sophisticated drilling equipment, the arch villain threatens to drill into Bond’s fusiform gyrus and thus destroy his ability to recognise faces. As well as further cementing the aforementioned oversimplification, an even graver offence, neuroanatomically speaking, is that the drill was pointed too low and was aimed at the mastoid process and not the fusiform gyrus. The Bond villain was subjected to a neurosurgical reprimand in Nature (16).

In addition to prosopagnosia, our patient also had difficulty recognising familiar places, so-called environmental agnosia. This symptom is closely linked to and often associated with prosopagnosia. As in prosopagnosia, it is the occipitotemporal connections that are affected, typically on the right side, although some patients have bilateral lesions. The patient can describe a place from memory or locate it on a map, but will fail to recognise the place once there and will lose their way. They thus have problems with the «what» aspect of their surroundings, but not the «where» (17). Our patient had no difficulty intellectually in understanding that she was inside the building that contained her office, but she experienced no feeling of recognition.

At a check-up a month later the patient had no symptoms other than occasional episodes of low-grade headache. As the association between steroid use and the CVT was uncertain, we considered the condition to be idiopathic and, in line with recommended practice, initiated 12 months of anticoagulation therapy with warfarin (18).

This case report illustrates an unusual clinical presentation of CVT, marked by curious cognitive symptoms that have also found their way into popular culture. As far as we are aware, this is the first report of prosopagnosia as a symptom of CVT.