Overview 

Miller Fisher syndrome (MFS) is a less common form of GBS and typically manifests with a combination of ataxia, areflexia, and ophthalmoplegia. MFS is often linked with the participation of the lower cranial and facial nerves and typically does not result in motor weakness of the limbs. Nevertheless, Miller Fisher subtypes have been characterized by weakness in the respiratory system and limbs. Another form of MFS is Bickerstaff brainstem encephalitis (BBE), characterized by changes in consciousness, coordination difficulties, weakness in eye movement, and unusual increased reflexes.¹

Clinical Presentation of Miller Fisher Syndrome 

Key clinical features

While not common, identifying MFS is crucial due to the confusion that may arise among clinicians with symptoms of ataxia and ophthalmoplegia, which can mimic signs of an upper motor neuron lesion or central origin. Additional neurological symptoms can complicate the clinical assessment process. An attentive doctor who performs a thorough neurological examination will discover the presence of areflexia, indicating that the main issue is in the peripheral nervous system. This evaluation should be initiated for demyelinating disorders and result in confirming MFS as the diagnosis if GQ1b auto-antibodies are present. Anyone showing symptoms of ataxia, areflexia, and ophthalmoplegia should have MFS considered in their differential diagnosis. ²

Differential diagnosis considerations

Guillain-Barré syndrome

Bickerstaff brainstem encephalitis

According to their categorization, Bickerstaff brainstem encephalitis is considered a variant of Miller-Fisher syndrome.

Acute ophthalmoparesis without ataxia

Brainstem strokes

Myasthenia gravis

brainstem encephalitis

Wernicke encephalopathy

Botulism

Tick paralysis³

Role of Electrophysiological Studies 

Sometimes, the existence of additional symptoms, the lack of Anti-GQ1b, and normal results on additional tests during the early stage of the syndrome can slow down the diagnosis process and lead to unnecessary requests for diagnostic tests. The neurophysiological examination during the acute phase showed a reduction in M response magnitude in both sides of the facial nerve and absence of blink reflex. Based on the clinical data, we decided to conduct additional studies on the central nervous system to eliminate the possibility of diving-related issues and other conditions such as cerebral venous sinus thrombosis. Although the symptoms were unusual and the Anti-GQ1b test came back negative, which is typically found in over 90% of MFS patients, the neurophysiological study results in the acute phase allowed for an early diagnosis and prompt treatment with immunomodulatory therapy.⁴

Nerve Conduction Studies (NCS) 

Nerve conduction tests were conducted using a Nicolet Viking IV Electromyographer following standardized procedures in our lab. Unusual findings in the NCS included reduced amplitudes of compound motor action potentials or sensory nerve action potentials, conduction block, prolonged distal latencies, slowing of nerve conduction velocity, or prolonged minimal F-wave latency. The investigation of the blink reflex was also observed.⁵

Electromyography (EMG) 

Assesses muscle reaction or electric signals when a nerve activates the muscle. The exam is utilized for identifying neuromuscular abnormalities. In the test, small needles (known as electrodes) are inserted through the skin into the muscle. The electrodes detect electrical activity which is shown on an oscilloscope, a device that displays electrical waves. An audio amplifier is utilized to make the activity audible. EMG tracks the muscle's electrical activity at rest, during light contraction, and when contracted forcefully. Muscle tissue is typically not active electrically when at rest. After inserting the electrode, there will be a short period of activity displayed on the oscilloscope, followed by the absence of any signal.⁶

Sensory Nerve Action Potential (SNAP) studies 

a necessary instrument for assessing the peripheral nervous system. The SNAP conveys details about the sensory nerve axon and its path from the skin's receptors to the dorsal root ganglia, helping identify if the nerve issue is due to axon loss or demyelination.⁷

Specific Electrophysiological Findings in Miller Fisher Syndrome 

The most common electrophysiological results seen in MFS include diminished sensory nerve action potentials and lack of H reflexes. Greater variability is observed in F waves and in different studies related to cranial structures. While routine neuroimaging typically does not show any abnormalities in MFS, some cases have shown contrast enhancement of nerve roots and signs of central nervous system involvement, which supports the theory of an anti-GQ1b-syndrome. This syndrome is considered a continuum that includes GBS, MFS, and Bickerstaff’s brainstem encephalitis. Due to the absence of randomized trials, treatments for GBS (such as intravenous immunoglobulin and plasmapheresis) are typically administered, despite retrospective analyses showing comparable results in both treated and untreated individuals. The prognosis of MFS is typically favorable with a mortality rate of less than 5%. In the small number of autopsy cases, macroscopic abnormalities weren't typically observed in the nervous system. Examination of the peripheral nervous system at a microscopic level (including cranial nerves) revealed segmental demyelination with slight perivascular infiltration, while the spinal cord and brain stem appeared normal.⁸

Limitations of Electrophysiological Studies 

Some definite reasons to avoid an electrophysiology study are:

• Blood infection or septicemia
• Acute worsening of heart failure not caused by an irregular heartbeat could lead to an irregular heartbeat
• Risk of severe bleeding (such as excessively high INR, DIC)
• Infection in the area or blood clot in the vessel where access is gained (such as femoral deep vein thrombosis or cellulitis in the lower limb)⁹

Summary 

• MFS is commonly associated with the involvement of the lower cranial and facial nerves and typically does not cause weakness in the arms and legs
• Nerve Conduction Studies:  Nerve conduction tests were carried out in our laboratory using a Nicolet Viking IV Electromyographer, following established protocols
• Abnormal results found in the NCS included decreased amplitudes of compound motor action potentials or sensory nerve action potentials, conduction block, extended distal latencies, slowed nerve conduction velocity, or extended minimal F-wave latency
• Studying Sensory Nerve Action Potentials is an essential tool for evaluating the peripheral nervous system
• The SNAP provides information on the sensory nerve axon's journey from the skin's receptors to the dorsal root ganglia, aiding in distinguishing between axon loss and demyelination as the cause of the nerve problem
• Common electrophysiological findings in Miller Fisher Syndrome consist of reduced sensory nerve action potentials and absence of H reflexes
• Although routine neuroimaging usually doesn't reveal any abnormalities in MFS, there have been instances where nerve roots show contrast enhancement and signs of central nervous system involvement, suggesting the presence of an anti-GQ1b-syndrome