Cortical Ribbon 7.0

Welcome back Ribbonites! We hope you’ve been thawing out from the bomb cyclone and snowball fights. This week’s version includes a whole host of Zebras as well as a Tapir or two. We hope you enjoy! As always, we welcome cases, images, comments, and haikus. If you haven’t already, don’t forget to sign up for the list-serve at the bottom left!


Case of the Week: Sneaky Susac

A male in his 40s was brought to the hospital by his family with complaints of “feeling foggy” and profound lethargy for a few months. Given these profoundly specific complaints, our detectives (aka JARS) jumped on the case immediately. His prior history was notable for a partial field cut from a retinal stroke and sensorineural hearing loss. He reports numerous prior steroid responsive episodes of confusional states. His exam was notable for mild executive dysfunction and left monocular inferior quadrantanopia, as well as mild gait instability without frank ataxia. His MRI scan is show below.

susac mri snowball

Is that splenium lesion tickling an old memory? We were sure intrigued with that atypical location! An example of his prior retinal exam showed these findings.

BRAO Susac.jpg

In addition to looking like a beautiful lightning bolt, this image demonstrates an occlusion of a branched retinal artery as seen by fluorescein angiography.   With this data at our disposal, our detectives felt they had the cat in the bag. Susacs it is!

Susac disease is a rare autoimmune disorder of the central nervous system characterized by a classic triad of branch retinal artery occlusion, sensorineural hearing loss, and encephalopathy. Notably, the encephalopathy can present in a multitude of ways, such as confusion, memory loss, behavioral disturbances, ataxia, dysarthria, paranoid psychosis, and headaches. Only described in 1979, it classically presents in women (3:1 ratio), but reports are limited to scattered case reports barely breaking 300 cases. Imaging is notable for lesions of the corpus callosum, especially the splenium. Additional areas such as the periventricular white matter, brainstem and cerebellum can also be affected. These may appear white on T2/Flair (new fluffy snowballs) and black on T1 (old black holes). Remember, the callosum is generally spared from vascular disease so lesions in this location are quite rare.

The pathology of Susac Disease derives from occlusions of precapillary arterioles of the brain, retina, and cochlea, but a specific biomarker has not been identified. Ophthalmologic examination with fluorescein angiography (FA) demonstrates pathology at branch retinal arteries. The encephalopathy can manifest in a number of ways, but tends to be steroid responsive. Rare and rarer disorders to consider in this scenario also include primary CNS vasculitis, CADASIL, Sarcoidosis, Marchiafava-Bignami (more to come soon!) as well as more common neurologic disorders such as Multiple Sclerosis or acute disseminated encephalomyelitis (ADEM). Finally, regarding prognosis, it is best to put on your MS thinking cap. Susac disease can be monophasic in about half the cases, but also presents as a polycyclic or rarely chronic continuous course. Immunosuppressive therapy is recommended, with drug agent dependent on attending de jour. Regarding our friend, he underwent a lumbar puncture which showed lymphocytic pleocytosis and he improved with a 5 day course of IV steroids. Rituximab was initiated upon discharge. Click on the links below for more learning.

Case Summary and Review

Radiology Images

Optho Images


Pediatric Pearls

Fall, Fever, Fright, OH MY!: The story of Vanishing White Matter Disease

Vanishing white matter (VWM) disease, also known as childhood ataxia with central hypomyelination is a white matter disease that classically leads to chronic neurologic deterioration dominated by cerebellar ataxia. Episodes of rapid neurologic deterioration are characteristically provoked by stresses such as fever, minor trauma (falls), and extreme fright.  Vanishing white matter disease has an autosomal recessive mode of inheritance.  It is one of the most prevalent inhereted childhood white matter disorders but its exact incidence is unknown.  Although it was initially believed to be only a childhood disease, VWM disease has also been discovered in the early infantile period, adolescents, and adults.  Typically the disease is less severe the older one initially presents. The most common variant of this disease is in childhood between the ages of 2-6 years old.

VWM Disease is believed to be caused by a defect in any of the five subunits of the  eukaryotic translation initiation factor eIF2B.  Interestingly glial cells are predominantly affected including oligodendrocytes and astrocytes, however neurons are spared.  As you may remember from medical school, eIF2B is required for the initiation of protein translation.  It is believed that a defect in eIF2B leads to glial cells that are hyper-reactive to stress, causes decreased protein synthesis and activates the unfolded-protein response (UPR) which causes cellular apoptosis and abnormal cell proliferation that ultimately leads to myelin destruction and abnormally functioning oligodendrocytes.

Classic Clinical Features

In the infantile form of VWM, the classic presentation is hypotonia followed by sudden onset of seizures, spasticity, developmental regression, and blindness.  These patients usually die by two years of age. The most common form, the childhood-onset form, is characterized by normal initial development followed by new onset ataxia between the ages of 2-5 years.  Episodes are brought on by fever, minor trauma, and extreme fright. Subsequently they have neurologic deterioration and develop worsening motor abilities, spasticity, hyper-reflexia, dysarthria, visual disturbances (optic atrophy) and seizures.  The time course of disease varies widely ranging from death within months to years after onset to some surviving for many years after onset of the disease. The adolescent and adults forms of the disease are generally more mild and progress much more slowly.

Diagnosis

Diagnosis is made by a combination of clinical presentation, characteristic MRI findings, and genetic testing.  The classic MRI findings include abnormal signal of almost all cerebral white matter with sparing of U-fibers, pars of the corpus callosum, internal capsules, cerebellar white matter (can be affected but not typically) and brainstem. The cortical gray matter is almost always spared.  There is no contrast enhancement which can help distinguish this disorder from other inherited leukodystrophies end encephalitides.  Overtime the MRI demonstrates progressive rarefaction and cystic degeneration of the affected white matter and the white matter becomes replaced with CSF.

VWMD

A: T2 weighted image showing diffuse white matter abnormality

B: T2 FLAIR imaging demonstrating progressive cystic degeneration

C: T1 weighted image showing the “stripped pattern” suggestive of remaining tissue strands of normal white matter

Treatment

Unfortunately there is no cure for this disease and treatment relies mostly on symptomatic management.   Avoidance of stressful situations, prevention of trauma (wearing a helmet), and preventing infections are important to prevent episodes of neurologic deterioration.  Physical therapy and occupational therapy are useful in regards to managing motor dysfunction.  AEDs are used for treatment of associated seizures.

See Below for More Information!

Genotype-phenotype correlation in vanishing white matter disease.
van der lei (Neurology 2010).

Bugiani J Neuropath (Exp Neurol 2010).

van der Knaap (Lancet Neurology 2006)


The Price is Rite Review

An uncommon presentation of a rare disease?

This week’s RITE review opens with a complicated, still unknown Pruitt-level case. A young man with diabetes, end stage renal disease on dialysis, peripheral vascular disease presents following a systemic infection with decreased mental status and global encephalopathy requiring intubation. He is not an alcoholic, but has a history of glucoses levels ranging from 50-500 from poor glucose control. T2 Flair shows the following:

Screen Shot 2018-01-28 at 10.33.27 AM

That’s a bright corpus callosum. The lesion was also DWI positive, but had no contrast enhancement. Further work up revealed bilateral retinal vasculitis, but no branch retinal occlusions. What is this? It seems unlikely to be vascular ischemic given the corpus draws blood supply from multiple different vascular territories. This might be Susacs, although he has no hearing loss and no true branch retinal artery occlusions. It could be CNS vasculitis, but conventional angiogram done a few days into the hospital stay was also negative. Could this actually be Marchiafava-Bignami syndrome?

In 1903, two Italian pathologists (Ettore Marchiafava and Amioc Bignami)  performed autopsies on a few men who were known alcoholics that died following progressive seizures and coma. These men were all found to have severe necrosis of the corpus callosum, bringing forth the disease now known as Marchiafava-Bignami syndrome. Fast forward more than a 100 years and neurologists are still searching for a true definition of this disease, proving clinical and radiographic heterogeneity is the rule more than the exception. Currently MBD is thought to have two subtypes. Subtype A involves the entire corpus callosum and has more profound features of coma, stupor and pyramidal tract symptoms. Subtype B is more mild with only partial involvement of the corpus and more mild clinical features. Radiographically, lesions are T1 hypointense and T2 hyperintense. Multiple case reports in the literature note the presence of restricted diffusion, although classically neuro-radiologists do not feel diffusion restriction is part of this syndrome. It is not clear that we truly understand what causes this, but the underlying pathology seems to be demyelination and necrosis of the corpus callosum, likely in association with malnutrition, thiamine, B12 and other nutritional deficiencies. There have also been a few case reports of nonalcoholic patients having MBD in the setting of rapid glucose changes from poorly controlled diabetes mellitus. Could our gentleman in this case have an uncommon presentation of an inherently rare disease? As much as I hate to leave you with a cliff-hanger, this one is still somewhat a mystery.


This is your Brain on Poetry – Weekly Neurology Haiku

EMG by Dr. Lauren Elman

Weak, Numb and Tingly
Electrodiagnostics
Gets you the answer

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