Case Of the Month 2 – Answer

 With great neurologic symptoms comes expansive differential diagnosis lists.  But lets just hone in on the key symptoms that suggest diagnoses that fit a little better with this patient.  This patient has ataxia, which indicates cerebellar involvement.  The ataxia in the patient appears to largely be truncal, which classically localizes to the vermis.  The gait seen in this type of ataxia is wide-based with normal coordination of the arms and legs but instability of the trunk (colloquially the “drunken sailor gait”). We also have ophthalmoplegia which is impairment of the extraocular muscles.  So already we have two affected neurologic areas which we need to find a uniting diagnosis.  A single or focal lesion is thus unlikely.  Diagnoses such as MS, toxic exposures causing neurologic impairment (such as heavy metals), metabolic derangements, neoplastic diseases (metastatic spread or paraneoplastic syndromes), autoinflammatory diseases, intracranial infections, and multi-infarct CVA are some choices that could affect multiple parts of the nervous system at once.  However this patient has a very rapid onset in symptoms without change in mental status and a paucity of other symptoms.  This makes diagnoses such as MS, Wernicke’s encephalitis, CVA, and autoimune demyelinating diseases more likely, although the others are still on the list.  Add in the preceding dysentery and this points us towards a very rare but classic presentation of Guillain-Barre Syndrome.

Here are some very nice videos highlighting the above symptoms, because describing them in text doesn’t do them justice:

Truncal ataxia – https://www.youtube.com/watch?v=ExSvRhqmXn8

Ophthalmoplegia – https://www.youtube.com/watch?v=FGJIpAPdb-c

The “classic” GBS that we know involves post-infectious ascending symmetric paralysis, however there are many subtypes of GBS that present in entirely different ways.  The subtypes are based on whether a demyelinating process or axonal process is occurring, and what the spectrum of symptoms are in the patient.  These subtypes frequently overlap and do not always consist of all the classic symptoms.  This patient presented with ophthalmoplegia, ataxia and areflexia, which is a classic triad of the Miller Fisher Syndrome (MFS) variant of GBS.  MFS occurs in about 1-5% of GBS patients in the western hemisphere and is more common in men than women (about two times more).  Ophthalmoplegia is frequently the initial presenting symptom, and the most commonly found symptom in MFS.  The pathogenesis largely revolves around autoantibodies formed due to molecular mimicry of a preceding infection, which then attack ganglioside and axonal molecules. Anti-GQ1b antibodies are more heavily implicated in MFS than other subtypes and in high enough titers in the CSF is diagnostic of the disease. Campylobacter jejuni is implicated in 30% of GBS cases and there are certain strains in particular that are associated with activation of anti-GQ1b antibodies.  There is a high density of GQ1b ganglioside in CN III, IV, and VI which likely explains the association of ophthalmoplegia with MFS.

 

Diagnosis starts with a high clinical suspicion as always, but any patient presenting with neurologic symptoms after a recent infectious process (e.g. diarrhea) should be at least considered for a GBS spectrum process, especially if motor weakness is involved.  Workup will involve sending labwork and possibly repeating a CT head to rule out other causes but the only somewhat diagnostic test in the ED is an LP.  If albuminocytologic dissocation is seen, the diagnosis is more likely, it will help guide inpatient treatment and you can help out your neurologists by sending anti-GQ1b titers at that time (they’ll come back later and help confirm the diagnosis).  The inpatient team can perform a MRI and EMG and their choosing.  Management is largely left to the inpatient service, as IVIG and plasmapheresis are the current treatment modalities, but the greater concern in the ED is diaphragmatic paralysis.  About 25% of GBS patients develop respiratory insufficiency and given that this patient has had symptoms for 6 days, he could be progressing to that point.  Furthermore, the patients that progress to respiratory failure also tend to show more autonomic instability due to autonomic nerves becoming affected.  This means this gentleman could drop his pressure suddenly, become bradycardic or slowly lose his ability to breathe.  He may already have a weakened diaphragm without us noticing it on physical exam. This is why it is critical for all GBS suspected patients to have a negative inspiratory force (NIF) and forced vital capacity (FVC) tested by a respiratory therapist.  NIF is normally 60 or greater, and as it approaches 20 you are most likely heading towards intubation.  Repeated testing is critical especially in patients with initial abnormal NIF and FVC.  Disposition is floor vs. ICU.  ICU candidates are any patients with signs of labile dysautonomia, FVC <20, a decreasing NIF, or signs of respiratory compromise.  With therapy, most patients recover from the classic triad completely, with mean improvement to active functional status at 10 weeks and complete recovery from areflexia at 6 months.