Introduction

Facial onset sensory
and motor neuronopathy (FOSMN) syndrome is an unusual neurodegenerative disorder
with less than 50 cases described in the world literature 1, 2. Developing in an inferior
to superior fashion, FOSMN’s disease begins at the cranium and gradually involves
the upper extremities. This distinctive pathology was first reported by Vucic et al. in 2006 with a case series in four
male patients, in which the disease was initially classified as paresthesia and
hypesthesia that serially developed in a craniocaudal route along the trigeminal
nerve 1, 2. In the few cases
reported in the literature, sensory integration deficits have been reported to
occur months, or years prior to motor neuron (MN) degeneration. Notably, a typical
MN deficit in FOSMN is the inability to perform a blink response 2. Other accompanying chronic
symptoms of the disease pathology include involuntary muscle dysfunction (e.g.,
speech production), lower MN impairment (e.g., muscle spasms, twitch, attenuation),
and weight decline 2.

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Possible causes of FOSMN are thought to be caused
secondary to Tangier’s disease, amyotrophic lateral sclerosis 3, 4, leprosy 5, ATP-binding cassette transporter mutations 6, and a variety of immune disorders 7, 8. Since the original report in 2006, 38 cases have since been described
with a male preponderance (25 males and 13 females, ratio = 1.92:1), a mean age
of 54.0 years (range = 38–77 years), and a disease tenure of 8.9 years
(range = 1.2–36 years)  2. Here, we present a
unique case of FOSMN, of the disease process uniquely restricted to the
craniofacial region, with no loss of motor function to the upper extremities.
To our knowledge, this clinical presentation has not been previously reported
in the literature.

 

Case
Report

            A 70-year-old
woman with a history of invasive ductal carcinoma stage IA two years prior to presentation
and Parkinson’s Disease, presented with a one-month history of progressive
facial hypesthesia, dysarthria and bilateral dysfunction of trigeminal and
hypoglossal nerves. Facial weakness progressed from grade III to grade IV over
a five-month period, initially affecting her lips, progressing to cheeks, then affecting
eye lid movement. Weakness was more severe on the right lower face than the left,
including an inability to shut her eyelids completely, inability to close her mouth,
and tongue weakness leading to an inability to eat.  Facial sensory loss was in a trigeminal
distribution affecting V1-V3 bilaterally. Electromyography and nerve conduction
studies demonstrated absent bilateral nasalis, R1, and R2 blink responses, with
fibrillations of motor units showing longer duration, higher amplitude, and
reduced recruitment. Results suggested chronic neuropathic facial nerve
changes.

On exam, the patient
had normal deep tendon reflexes. Laboratory results demonstrated normal cerebrospinal
fluid (CSF) with negative cytology, and negative ANCA, ACE (serum and CSF), and
Lyme disease titers. Rheumatologic evaluation for Sjogren’s syndrome demonstrated
a negative SS-A and SS-B antibodies. Magnetic resonance imaging (MRI) of parotid,
brain, and auditory canal was within normal limits. Given the slow onset of
facial paralysis progression and hypesthesia a diagnosis of Bell’s Palsy was
ruled out. Intravenous immunoglobulin (IVIG) treatment lead to temporary relief
of hypesthesia.

Discussion

FOSMN is an unusual and
gradual motor neuron (MN) disorder classified by facial sensory aberrations and
involuntary muscle deficits. Vucic et al.
(2006) originally reported on a case series of four Caucasian males with muted sensory
nerve action potential (SNAP) and compound muscle action potential (CMAP)
amplitudes, along with axonal neuropathy along the cranial nerves 1. Our current case
closely resembles these early findings of FOSMN. However, in this current case,
we describe a patient with FOSMN characterized by MN degeneration limited
solely to the craniofacial region, not serially progressing to the upper
extremities. This is a unique presentation given that other demonstrated MN
deficit affecting the upper limbs. OM1 8. Other potential MN
disease pathologies such as Bell’s Palsy, ALS, Sjogren’s syndrome, and others were
omitted after review of the clinical dysfunctions, electrophysiology, and laboratory
results.

Electrophysiological measurements,
including nerve conduction studies, have previously described reduced SNAP amplitudes
and less notably reduced sciatic nerve CMAP amplitudes in the upper extremities 1, 7, 9, 10. Previous studies have
found degradation of myelinated cranial nerve V fibers, while retaining those
of unmyelinated structures 11. Moreover,
electrophysiology has been used to characterize irregular reflexes in patients,
whether discontinuous or loss of R2 unconditioned reflexes in those patients
suspected of having FOSMN 12. Laboratory samples (e.g.,
blood chemistry and CSF workup) are typically within range, but antibody
positivity (e.g., anti-myelin-associated glycoprotein anti-MAG,
anti-sulfo-glucuronyl paragloboside anti-SGPG, anti-sulfatide antibodies,
anti-nuclear antibodies, anti-Ro antibodies, and anti-GD1b antibodies) have
been abnormal in a few clinical cases from the literature, pointing towards a primary
immune biogenesis 1, 8, 13-15. Additionally, radiologic
imaging is commonly normal as well, although cervical spine shrinkage has been
observed 2. Post mortem histology
can show discernable nuclei cell atrophy at the level of the brainstem and
spinal cord, which can affect the fifth (V), seventh (VII), and twelfth (XII)
cranial nerves, due to myelin deterioration 1. Lastly, genetic sequencing
has not found an associated gene locus 3, 8.  

Lines of treatment for
FOSMN is often imperfect due to the rarity of this MN disorder 2. A recent review has
shown no proven successful treatment exists given the small cohort of patients
described in literature 2. However, promising outcomes
have been demonstrated with IVIG or plasmapheresis therapies 7, 15, as with our patient
reported here.

FOSMN’s etiology is
still under preclinical and clinical investigations. These lines of research
will not only shed light on the disease pathogenesis, but also potentially provide
new, safe, and efficacious treatments for patients progressively developing
this debilitating disease. Additionally, FOSMN may be discerned as a systemic neurodegenerative
disease, as is the case with many neurodegenerative disorders. The initial clinical
description of FOSMN as a neurodegenerative disorder was due observing the reduced
presence of pro-inflammatory cells (e.g., macrophages, microglia) surrounding
the affected tissues and no obvious clinical enhancements following immunotherapy
1, 14. However, some reported
cases have seen improvements in clinical symptoms following immunotherapies, as
is the case with our patient reported here, raising the possibility of FOSMN to
be an autoimmune neurodegenerative disorder.

 

Conclusion

FOSMN is a unique gradual
motor neuron disorder described by facial onset sensory abnormalities. In our
case, progressive left-sided facial paralysis and hypoesthesia due to FOSM was
restricted to the craniofacial region with no upper limb involvement, and
symptoms improving with the use of IVIG. Although pathophysiological mechanisms
remain unclear, neurodegenerative and autoimmune mechanisms are proposed, with
our study strongly suggesting an immunologic mechanism.

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