Miller Fisher syndrome

Pathogenetic link and anti-GQ1b spectrum

Miller Fisher syndrome is viewed in modern neurology not merely as an isolated pathology, but as part of a single disease spectrum. The main unifying factor is the presence of specific immunoglobulins — anti-GQ1b IgG antibodies.

This same group includes a rare localized brainstem encephalitis — Bickerstaff brainstem encephalitis (Bickerstaff encephalitis, BE). Due to their shared immunological nature, these conditions may share similar features; however, their fundamental difference lies in the level of the nervous system lesion. While in Miller Fisher syndrome the pathological process exclusively affects the peripheral nervous system (PNS), Bickerstaff encephalitis is a disease of the central nervous system (CNS).

Clinical features and differential diagnosis

The key clinical marker that allows distinguishing Miller Fisher syndrome from the related Bickerstaff encephalitis is the state of tendon reflexes.

• In Miller Fisher syndrome, reflexes are always significantly diminished (hyporeflexia) or completely absent (areflexia). This is a classic manifestation of peripheral nerve damage.
• In Bickerstaff encephalitis, reflexes remain variable. In addition, the clinical picture of encephalitis typically includes ataxia and ophthalmoparesis against the background of a preceding febrile illness.

Magnetic resonance imaging (MRI) also aids in differentiation. In Bickerstaff encephalitis, the findings are nonspecific, but T2-weighted images reveal an extensive hyperintense lesion affecting the midbrain and pons, and sometimes the thalamus and basal ganglia. The prognosis is favorable, with clinical improvement clearly correlating with the resolution of MRI lesions. The absence of oligoclonal bands in the cerebrospinal fluid (CSF) and the complete resolution of symptoms point to an inflammatory nature, making true demyelination unlikely.

Also, when conducting differential diagnosis, it is important to rule out acute disseminated encephalomyelitis (ADEM). This is a severe immune-mediated inflammatory demyelinating CNS disorder that predominantly affects the white matter of the brain and spinal cord. ADEM is more common in children (peak in early childhood) and has a monophasic course. On MRI, the lesions are often large, patchy, with indistinct margins, involving the subcortical and central white matter. Spinal cord involvement occurs in a third of patients (mainly in the thoracic region) as longitudinally extensive transverse myelitis. If a second encephalopathic episode occurs after a prior ADEM, the disease is considered chronic (most commonly multiple sclerosis or neuromyelitis optica spectrum disorder).

Assessment of disability in polyneuropathies

In the diagnosis of immune-mediated peripheral nervous system disorders (including Guillain-Barré syndrome, which is often considered alongside Miller Fisher syndrome), the I-RODS (Inflammatory Rasch-built Overall Disability Scale) scale is used.

This is an official validated questionnaire designed to assess the impact of polyneuropathy on the performance of daily activities and social participation. The target group includes patients with Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), and polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUS).

Completion method:

• The format involves patient self-administration (Patient-reported outcome).
• The patient assesses the degree of limitation in their daily activities.
• To answer, select one option in the corresponding column (place a cross).

Interpretation of results: scores are evaluated in points. There is a direct correlation: the higher the score, the fewer limitations the patient experiences, indicating a more preserved functional status.

Superacute forms of encephalomyelitis

Since Miller Fisher syndrome requires the careful exclusion of CNS pathologies, it is important for a neurologist to remember superacute forms of inflammatory diseases. The most severe variant of acute disseminated encephalomyelitis is considered to be acute hemorrhagic leukoencephalitis (Hurst disease).

This rare disease can occur at any age. It usually develops following influenza or an upper respiratory tract infection. The clinical picture is characterized by a sudden onset of fever, nuchal rigidity, hemiplegia, aphasia, brainstem dysfunction, seizures, and rapid impairment of consciousness. Unfortunately, the disease is generally fatal.

The pathomorphological picture at autopsy is specific:

• The brain is hyperemic and edematous (sometimes asymmetrically), with herniation frequently observed.
• Multiple petechial hemorrhages are identified diffusely throughout the brain.
• Perivascular lesions are formed: ball- or ring-shaped hemorrhages around necrotic venules (sometimes with fibrinous exudate).
• Perivenous demyelinating lesions with a marked neutrophilic infiltrate are present.

Unlike classic ADEM, where lymphocytes predominate in the CSF, Hurst disease shows pleocytosis with a predominance of polymorphonuclear cells (neutrophils).

Class and exam questions

What else to study on this topic

• Bickerstaff brainstem encephalitis: MRI findings and prognosis
• Acute disseminated encephalomyelitis (ADEM) in children
• Hurst disease (acute hemorrhagic leukoencephalitis)
• I-RODS scale: completion method and interpretation
• Differential diagnosis of recurrent ADEM and multiple sclerosis

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.