Medical students say that Neurology is the discipline of medicine that exalts the memorization of foreign words and eponyms.  In Neurology there are endless facts surrounding names that go back hundreds of years and whose history and meaning are lost to us.  Whenever a Neurologist gets bored of learning thousand of terms in neuroanatomy he still faces the equally daunting challenge of learning an impressive barrage of signs, symptoms, syndromes, and diseases.  I usually know which ones of these my first, second, third, and fourth year residents are apt to recognize and which ones they won’t.  Still there are some that make most fellows and faculty members draw a blank.  My favorite among strange syndromes is the Urbach-Wiether disease (named after Erich Urbach and Camilo Wiethe). Just in case you are not enthralled with the eponym you may try memorizing its rather cryptic synonyms: “lipoid protenoisis” or “hyalinosis cutis et mucosae”.

 First of all, Urbach-Wiether is a disease not a syndrome. This means that we have one cause (i.e., a genetic mutation in chromosome 1 inherited in autosomal recessive fashion) that explains all of the symptoms of the condition. Both sexes are affected equally. The mutation affects a protein in the extracellular space (also called matrix) that is present in all tissues and organs.  The role of this extracellular matrix is to provide a scaffold to the cells and a nidus for important biochemical reactions. In previous blogs I have spoken about several conditions where elements of the matrix appear affected (e.g., Ehlers-Danlos, Marfan, Lujan-Fryns syndrome) (see:  http://bit.ly/167eZuR ). A high percentage of individuals affected with these conditions exhibit autistic manifestations.

The Urbach-Wiether disease is usually recognized for its dermatological (skin) manifestations.  Affected individuals have poor wound healing, dry and wrinkly skin, and a yellowish infiltrate of the lips, tonsils, and epiglottis.  Beading (the formation of nodules) around the eyelids is common (sse Figure).  Hoarseness may be progressive and permanent.  There is no cure for the condition.

Figure: Yellowish white deposits of the eyelids are commonly seen in Urbach-Wiethe disease. Eyelashes are preserved. These deposits are evident throughout the skin, mucosa, and internal organs of the body.

Figure: Magnetic resonance imaging of a patient with Urbach-Wiethe disease. Selective mineralization of the amygdala is seen as loss of signal (circles outlined in blue).

In this blog we will concentrate on patterns of behaviors seen in Urbach-Wiethe disease that start from infancy.  Manifestations of the disease include seizures, psychotic behaviors (like in schizophrenia) and mood disorders (anxiety and depression). Many of these are considered the consequence of damage to a structure of the brain called the amygdala (amygdala is singular and amygdalae is the plural form).  The amygdala is an almond-shaped island of gray matter in the anterior portion of the temporal lobes.  It is part of the limbic system and thus plays a major role in processing emotional reactions. In Urbach-Wiethe disease blood vessels within the amygdalae become mineralized and hardened. The lack of proper oxygen exchange with surrounding tissue damages the amygdalae in a progressive manner, meaning that symptoms develop over time.

According to Kandel, “…the major consequence of damage to the amygdala is an inappropriate response to ambiguous social cues and an inability to respond to any threat inherent in a situation” (Kandel, 2012, p. 360). Patients with damage to their amygdala can’t read emotions in other people faces. They do not know when other people are afraid or when they themselves should be afraid. Not being able to read emotions in others makes them accept things at face value.  In effect, some patients are extremely trusting or gullible.  Being both credulous and unable to intuitively realize when they are in danger can provide for dire consequences.

Patients with Urbach-Wiethe disease have a normal IQ, good language and perception skills. These suggests that besides the amygdala most other parts of the brain appear to be normal. Indeed, patients with Urbach-Wiethe disease lack emotional recognition in the facial gestures of others while having completely intact visual pathways. They are able to recognize familiar faces in photographs meaning that face recognition is therefore not impaired.

The amygdalae have major connections with the frontal lobe. This structure serves therefore to link emotions to the executive abilities of the brain. A few years ago the neuroscientist Antonio Damasio (see reference) studied patients with Urbach-Wiethe disease and found that they had difficulties in making decisions. They could describe a problem in logical form but could not decide between the various pros and cons the escenario provided. In this regard affected patients may partake in a monotonous existence that abhors change in the environment.

Many of the above mentioned symptoms offer some resemblance to those observed in autism.  This has promoted an «amygdala theory» of autism (Baron-Cohen, 2000). Lesions of the amygdala do not cause autism but it is presumed that disturbances in connectivity to this structure may in some way be related to the condition. Thus far functional imaging studies have failed to show consistent deficits in activation of the amygdala in autism spectrum disorders. Furthermore, postmortem studies on the amygdala have been based on small series patients and have provided diverging findings.

References

Baron-Cohen S, Ring HA, Bullmore ET, Wheelwright S, Ashwin C, Williams SC. The amygdala theory of autism. Neurosci Biobehav Rev 24(3):355-64, 2000.

Damasio A. Descarte’s Error. Penguin Books, 2005.

Kandel ER. The Age of Insight. Random House, New York, 2012.