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The advent of non-invasive imaging has revolutionised in vivo diagnosis of many medical conditions. This is exemplified by the use of MR scanning of the brain in the investigation of neurological disease. Historically, many pathological conditions have been described in terms of their resemblance to foods, for example: sago spleen (amyloid deposition); nutmeg liver (chronic venous congestion); anchovy sauce liver (amoebic abscess); popcorn cell (Hodgkin’s disease); and strawberry gall bladder (cholesterolosis).1 The imaging revolution appears however to have heralded a metaphorical change, with an increasing tendency to describe scan appearances in terms of animate objects. There is now it seems a “neurological MRI menagerie”, and it is expanding.
PROGRESSIVE SUPRANUCLEAR PALSY: THE HUMMINGBIRD OR PENGUIN SIGN, AND THE MICKEY MOUSE SIGN
Progressive supranuclear palsy (PSP), an atypical parkinsonian syndrome previously known as the Steele-Richardson-Olszewski syndrome, has a prevalence of ∼5/100,000. Characteristic features include the insidious development in middle age of early postural instability leading to falls; a vertical supranuclear gaze palsy; axial rigidity; staring facies with a reduced blink rate; and a frontal dysexecutive syndrome.2 At the moment, the diagnosis remains clinical, and differentiating PSP from Parkinson’s disease and other neurodegenerative disorders including multiple system atrophy may not be straightforward. However, certain MRI features may provide support for the diagnosis: on mid-sagittal MRI views, atrophy of the mid-brain tegmentum with relative preservation of the pons leads to an appearance that has, perhaps reflecting a degree of zoological controversy, been described both as the “hummingbird sign”3 and the “penguin sign”4 (fig 1A). On axial MRI views, the “Mickey Mouse sign” similarly reflects fairly selective atrophy of the midbrain tegmentum, with relative preservation of the tectum and cerebral peduncles (fig 1B).
WILSON’S DISEASE: THE FACE OF THE GIANT PANDA SIGN
Wilson’s disease, an autosomal recessive disorder of copper metabolism, results in copper deposition within liver, brain and other organs. The neurological features include tremor, dysarthria, dysphagia, dystonia, writing difficulty, cognitive decline, gait impairment, chorea and seizures.5 Early diagnosis is essential, as treatment with copper chelating agents may reverse symptoms and prevent progression; this depends on the demonstration of low serum caeruloplasmin, excess urinary copper excretion and the presence of corneal Kayser-Fleischer rings which are seen in at least 98% of cases of neurological Wilson’s disease.5 MRI appearances include signal change and atrophy in the basal ganglia, cerebral white matter and infratentorial structures, sometimes leading to the “face of the giant panda” sign reflecting hyperintensity in the midbrain tegmentum with relative sparing of the red nuclei (eyes), part of the pars reticulata of the substantia nigra (ears), and the hypointensity of the superior colliculus (mouth) (fig 2A).6 On occasions, the giant panda may be accompanied by her “cub”,7 also termed the “face of the miniature panda”8 sign in which similar appearances are seen within the pontine tegmentum (fig 2B).
PANTOTHENATE KINASE-ASSOCIATED NEURODEGENERATION: THE EYE OF THE TIGER SIGN
A number of rare disorders associated with excess iron deposition within the basal ganglia are now recognised, and have recently been reclassified under the umbrella term of “neurodegeneration with brain iron accumulation”. The commonest of these rare disorders, pantothenate kinase-associated neurodegeneration (PKAN) (previously known as Hallervorden-Spatz disease9) is an autosomal recessive condition resulting from mutations in the PANK2 gene.10 Patients present with combinations of dystonia, parkinsonism, speech abnormalities and psychiatric disturbance. On T2-weighted MRI, virtually all cases with PANK2 mutations described to date are said to have the “eye of the tiger sign”, reflecting a central area of hyperintensity (possibly due to tissue necrosis and oedema) within the medial globus pallidus which is hypointense due to iron deposition (fig 3).10 Initial claims of perfect sensitivity and specificity of this sign for the PANK2 mutation have recently been challenged, with the description of a disappearing “eye of the tiger” in a case of genetically confirmed PKAN,11 and conversely the presence of the “eye of the tiger” in cases without an identified PANK2 mutation12 and pathologically confirmed PSP.13
ALZHEIMER’S DISEASE: THE ELEPHANT SIGN
Alzheimer’s disease, the commonest cause of dementia in the developed world, is typically associated with insidious onset of episodic memory impairment, followed by the accumulation of deficits in other cognitive domains.14 A definite diagnosis depends on the histopathological demonstration of excess deposition of extracellular amyloid plaques and intraneuronal tangles composed of phosphorylated tau. Accumulation of these abnormal proteins leads to neuronal cell death which may be visualised as atrophy on MRI.15 Medial temporal lobe structures, including the entorhinal cortices and hippocampi, whose resemblance to seahorses led to their name (hippocampus being Greek for seahorse), are affected early in the disease process. Qualitative visual measures of medial temporal lobe atrophy have predictive value for which patients with mild memory impairments will progress to develop Alzheimer’s disease.16 Although to my knowledge not previously described, during the progression of atrophy as each hippocampus decreases in size and the hippocampal fissure becomes more prominent, the hippocampi sometimes come to resemble sitting elephants (fig 4). It is however unlikely that this “elephant sign” is specific for Alzheimer’s as hippocampal atrophy is also seen in other neurodegenerative diseases including frontotemporal lobar degeneration.17
LEUCODYSTROPHIES: “TIGROID” AND “LEOPARD SKIN” APPEARANCES
The leucodystrophies comprise a range of rare disorders of white matter. Metachromatic leucodystrophy, an autosomal recessive disorder of myelin metabolism, results from a deficiency of the enzyme arylsulphatase A, leading to the deposition of sulfatides in the central and peripheral nervous systems as well as in other organs. Metachromatic leucodystrophy is usually divided into infantile, childhood and adult onset forms with cognitive changes, ataxia and significantly reduced life expectancy common to all. On MRI the typical appearances are of diffuse symmetrical high signal in cerebral white matter on T2, FLAIR and proton density MRI. Occasionally, relatively hypointense signal abnormalities within the demyelinated white matter may be seen: when these are present in a radiating pattern they have been described as “tigroid” (fig 5A), and when punctuate in appearance as “leopard-skin” (fig 5B).18,19 These findings are thought to represent areas of relative sparing of myelin and/or focal areas of lipid deposition.20 The tigroid pattern is however not specific for metachromatic leucodystrophy; it has also been described in other leucodystrophies including X-linked Pelizaeus–Merzbacher disease21 and autosomal recessive Krabbe’s disease.20
MALIGNANT CENTRAL NERVOUS SYSTEM TUMOUR: BUTTERFLY GLIOMA
The diagnosis of central nervous system tumours has been revolutionised with non-invasive imaging, and especially MRI. Although definitive diagnosis still depends on histopathology, MRI may provide important diagnostic clues as to the likely diagnosis, and allows for stereotactic (stealth) biopsy of focal lesions. A so-called “butterfly” glioma, involving both cerebral hemispheres, linked via the corpus callosum (fig 6) is highly suggestive of a high grade astrocytoma, although such appearances have rarely been reported in the context of other pathologies including neuronal ceroid lipofuscinosis.22
CONCLUSIONS
Despite a trend to move away from the use of eponymous disease names, metaphorical descriptions of imaging appearances continue to thrive. Although a number of neurological diseases are associated with inanimate MRI signs—for example, the “hot cross bun” sign of multiple system atrophy,23 and the “molar tooth sign” of Joubert syndrome,24 the apparently increasing number of animate descriptive terms is striking. Whether this vogue reflects a natural tendency for humans to visualise animate over inanimate objects, an unrecognised biological relation between neuropathology and zoology, or is merely due to chance is unresolved. Nonetheless, in neurological practice, as in other fields of medicine, recognising patterns of MRI abnormality is an increasingly important part of the diagnostic process, and if nothing more, animal-based descriptions appear to be useful aides-mémoire.
The neurological MRI menagerie at a glance
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“Hummingbird” and “Mickey Mouse” signs of progressive supranuclear palsy
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“Face of the giant panda” sign of Wilson’s disease
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“Eye of the tiger” sign of pantothenate kinase-associated neurodegeneration
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“Elephant” sign of Alzheimer’s disease
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“Tigroid” and “leopard skin” appearances in leucodystrophy
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“Butterfly” glioma
Acknowledgments
I am grateful to Dr Dominic Paviour, Dr Rachael Scahill and Ms Sarah Levy for providing images; to Professor Nick Fox and Dr Rachael Scahill for discussions about the “elephant sign”; and to Dr Anette Schrag for her helpful comments on the manuscript.
REFERENCES
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