If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Facial palsy is clinically defined as peripheral (pFP) or central (cFP).
•
The definition of the facial palsy (FP) suggests the differential diagnosis.
•
pFP may originate from a pons lesion in patients with multiple sclerosis (MS).
•
A cortex lesion may determine a clinically defined pFP in MS patients.
•
In presence of a pFP an MRI should be performed before starting steroid treatment.
Abstract
Background
Diagnosis of central or peripheral facial palsy (FP) is traditionally based on clinical evaluation. This study aims at investigating the relationship between clinical evaluation of FP and lesion location as visible on Magnetic Resonance Imaging (MRI) in patients with Multiple Sclerosis (MS) for the purpose of adding supporting evidence to the diagnosis of central or peripheral FP in these patients.
Methods
A retrospective study was conducted on data from patients who underwent MS treatment between January 2016 and January 2019 at the MS Center of Wayne State University, MI, USA, and presented with at least one episode of FP during the observational period. The following data was collected from each patient: demographics, time from MS onset, side of FP, FP type (central or peripheral, as clinically evaluated), FP onset, FP treatment, amount of recovery of normal facial movements, time elapsed from beginning of FP treatment, number of FP recurrences, lesions presence/absence and location as visible on MRI. Correlation analysis was performed to assess to which extent clinical evaluation of FP correlated with presence of MRI lesions in different locations.
Results
Eighteen patients were included in this study. In thirteen patients (72.2%) FP was classified as peripheral. Among them only five (38.4%) displayed one or more lesions in the pons. Correlation between presence of lesions in the pons and presence of peripheral FP was statistically significant (p = 0.02). Correlation between presence of lesions in the cortex (observed in 61.5% of patients with FP clinically evaluated as peripheral) and presence of FP clinically evaluated as peripheral was also statistically significant (p = 0.01). Finally, presence of lesions in the cortex was significantly correlated with presence of FP clinically evaluated as central (p = 0.02).
Conclusions
FP clinically classified as peripheral may be caused by central lesions in the cortex or pons and not only by peripheral facial nerve damage. In MS patients, FP may appear at the onset of the disease and be misdiagnosed as Bell ’s palsy. Clinicians should carefully approach FP diagnosis and perform a brain as well as temporal bone MRI before pursuing pharmacological treatment.
Di Stadio A., Dipietro L., Ralli M., Meneghello F., Minni A., Greco A., Stabile M.R., Bernitsas E.Eur rev med pharmacol sci sudden hearing loss as an early detector of multiple sclerosis: a systematic review. 2018a;22 :4611–4624. doi: 10.26355/eurrev_201807_15520.
). When a widespread lesion affects cochlear and vestibular nuclei, which are close to the facial nuclei, the patient may present with additional symptoms such as vertigo or hearing impairment (
Di Stadio A., Dipietro L., Ralli M., Meneghello F., Minni A., Greco A., Stabile M.R., Bernitsas E.Eur rev med pharmacol sci sudden hearing loss as an early detector of multiple sclerosis: a systematic review. 2018a;22 :4611–4624. doi: 10.26355/eurrev_201807_15520.
While in MS patients FP may arise from lesions in either central or peripheral pathways, pinning down the actual origin of FP via clinical examination in these patients is a particularly complex and prone to errors task. Clinically, FP is labeled of central origin if it affects the muscles of the II and III of the face (zygomatic, orbicularis oris, buccinator, mentalis, and platysma) (
) and of peripheral origin if it affects all facial muscles. Thus, it is well known that FP of central origin is caused by lesions above the level of the facial nucleus (in the pons -which belongs to the brainstem- of the contralateral hemisphere or in the cortex) and FP of peripheral origin is caused by lesions of the ipsilateral facial nerve, usually at the level of the geniculate ganglion (located in the facial canal). Unfortunately, such a definition of central and peripheral FP captures only marginally what is observed in MS patients. In fact, patients who present with FP clinically defined as peripheral can display lesions in areas of the CNS not extending to the root entry zone (REZ) (
) . Such limitations in the clinical definition of FP have implications in clinical practice. For example, based on the above clinical definition, a FP that is clinically diagnosed as peripheral but in fact is caused by a lesion in the CNS may be misdiagnosed as Bell's Palsy (BP) (a condition caused by damage in the peripheral facial nerve, which is typically treated with corticosteroids without having the patient undergo magnetic resonance imaging (MRI)). The fact that BP typically resolves with corticosteroid treatment, which is also the standard treatment for relapsing MS, further contributes to misdiagnosis.
This study aims at investigating the relationship between FP types as clinically evaluated and underlying MS lesion locations. Specifically, we aimed at investigating whether in MS patients presenting with FP, MRI can help uncover the origin of FP. To this end, we enrolled 18 MS patients who presented with FP (primary and recurrent). We examined and compared clinical findings (supporting either a central or peripheral origin of FP) with MRI results.
2. Materials and method
This retrospective, case series study was conducted at the MS Center of the Wayne State University, Detroit, USA and was approved by the local Institutional Review Board (IRB). Informed, written consent was obtained from all study participants.
Clinical records of patients under MS treatment between January 2016 and January 2019 were reviewed and patients who presented with at least one episode of FP were selected. The MS diagnosis was performed following the McDonald 2010 diagnostic criteria (
The diagnosis of FP was initially based on clinical observation only and was not supported by MRI findings. Namely, the FP was labeled as “central” if the paralysis involved the middle/low part of the face and “peripheral” if the paralysis affected all muscles of the hemiface.
The following data was collected for each patient: demographics, time from MS onset, side of FP, FP type (central or peripheral, as clinically evaluated), FP onset (which was defined as “early” when FP presented early on in the disease among the initial MS symptoms and as “late” when FP presented later in a patient with a known history of MS), FP treatment, amount of recovery of normal facial movements as measured by the ADS scale (
), time elapsed from the FP treatment, and number of FP recurrences.
A 1.5 Tesla brain and temporal bone MRIs (Philips Medical System Achieva scan, Philips, Best, the Netherlands) was acquired from each patient. Analysis of T2 MRI sequences was performed by a neuro-radiologist and aimed at identifying the presence/absence of lesions and their location. In patients with known history of MS, the most recent MRI was compared with the previous MRI scans to assess if new lesions were present.
2.1 Statistical analysis
A Chi (χ)-square test was used to assess the correlation between presence of lesions in the pons and presence of clinically defined peripheral FP. Similarly, a χ-square test was used to assess the correlation between presence of lesions in the cortex and presence of peripheral FP and between presence of lesions in the cortex and presence of central FP. The level of significance for all tests was set to 0.05. All analyses were performed with Stata ®.
3. RESULTS
3.1 Demographics
The data from N = 18 patients (N = 11 females and N = 7 males; average age 47.4 years, standard deviation (SD) 10.8 years; time from MS onset 12.3 years, SD 7.9 years (CI 95%: 0–27)) were analyzed. All patients suffered from at least one episode of FP (central or peripheral) during the observational period. One patient suffered from primary progressive (PP) MS (5.5%), three from secondary progressive (SP) MS with relapses (16.6%), and 14 from relapsing remitting (RR) MS (Table 1).
Table 1The table summarizes the patients’ demographics and MS features.
The left side was the most affected side of the face (11 out of 18 patients presented with left FP). In five patients, FP was clinically diagnosed as of central origin (27.7%) (cFP) and in 13 as of peripheral origin (72.3%) (pFP). Among patients with pFP, none presented any symptom other than alteration of facial motility; also, pFP severity score was lower than 5 as measured by the ADS scale. Specifically, one patient (7.7%) had a score of 4.7; five patients (38.4%) had a score between 1.5 and 3.9 ( 2.34 ± 0.93); and seven patients (53.9%) had a score between 0 and 1.2 (0.6 ± 0.4). Among all patients, in 4 patients (27.7%) FP onset was early (in one patient FP presented during the first year from the MS diagnosis and in three patients FP was the only presenting symptom of MS) . In 14 patients (72.3%), the FP onset was late (at least two years after their MS diagnosis). Among the patients with early FP onset, 3 were clinically diagnosed with pFP (Fig. 1) and 1 with cFP; among the patients with late FP onset, 4 were clinically diagnosed with cFP and 10 with pFP. In the latter patients, demyelinating lesions spread in the brain (Table 2) were present, which were not visible in their previous MRI.
Fig. 1The image shows the prevalence of the different clinical aspect (peripheral o central) in case of early (as presenting symptom) or late onset of MS.
Table 2Distribution of the lesions in the different part of CNS in our data sample. Patients who presented with FP as initial and only symptom of MS are in b.
Patient#
Type and side of FP
Lesion locations (from MRI)
Central
Peripheral
1
Left
Left side of pons
2
Left
Left side of pons
3
Right
Right side of pons
4
Left
Diffused in the cortex, not involving brainstem
5
Right
Diffused in cortex and brainstem
6
Right
Right side of midbrain and pons (small lesion)
7
Left
Left side of cortex, not involving brainstem
8
Left
Left side of subcortex only, not involving brainstem
9
Left
Diffused cortex and brainstem
10
Right
Diffused in cortex, not involving brainstem
11
Left
Left side of pons
12
Left
Left side of subcortex, not involving brainstem
13
Left
Left side of cortex (para atrial occipital)
14
Right
Left side of pons (tegmen) and brainstem (paraoccipital)
15
Left
Diffused in cortex (periventricular) and hypotrophy of corpus callosusm
16
Left
Diffused in cortex (iuxatacortical) with nuclei involvement(semioval and centromedullar)
17
Right
Diffused in cortical nuclei (semioval and periventricular), cerebellum, and brainstem
In the three patients in whom FP was the presenting symptom of MS (patient 1, 6, and 8), FP showed the typical clinical signs of pFP, i.e. hemifacial palsy affecting all the muscles of the three facial districts (upper, middle and low face) (Di Stadio 2016). pFP severity was 0 for patient 1, 0.9 for patient 6, and 1.2 for patient 8 as measured by the ADS score (see Table 2, in bold).
The FP as presenting symptom was initially diagnosed as stroke sequelae in one patient (cFP), and as Bell's palsy (BP) in three patients (16.7%) (pFP).
In all patients, FP (cFP and pFP) was treated with a high dose of oral corticosteroids for 10 consecutive days. Most patients (N = 14) completely recovered within 6 months, and four (3 with cFP and 1 with pFP) only partially recovered (Fig. 2) and still displayed facial asymmetry 12 months after the FP onset.
Fig. 2The image shows the prevalence of patients who partially or completely recovered their facial movements within 6 months after the onset of FP.
Twelve patients (66.7%, 3 with cFP and 9 with pFP) suffered from a single episode of FP while in six patients (2 with cFP and 4 with pFP) FP recurred; in 4 of them (66.6%) FP always recurred on the same side of the first event and in 2 patients (33.4%) FP recurred on the opposite side (Fig. 3A and B).
Fig. 3Panel A) Most of our patients presented with a single episode of FP during the observational period. Panel B) When FP recurred, it typically re-occurred on the same facial side of the first episode.
All patients presented with white matter lesions in the brain. None of the patients showed a hyperintense signal in the facial nerve tract from the ponto-cerebellum angle (APC) to the stylomastoid foramen (indicative of a peripheral facial nerve involvement) in the temporal MRI. Table 2 summarizes lesions location as visible in the MRI and type of FP as clinically evaluated.
Six patients (33.3%) displayed a pontine lesion (Fig. 4); in five of them FP was clinically evaluated as pFP and in one patient as cFP (Fig. 1). In 9 patients (50%) the lesions were observed only in the cortex with no involvement of the brainstem (Fig. 5); in 7 of them (77%), FP was clinically diagnosed as pFP and in 2 (23%) as cFP. Three patients (16.6%) had lesions both in the cortex and brainstem; in 2 of them FP was clinically evaluated as cFP and in one as pFP.
Fig. 4MRI of a patient that presents pons lesion with a clinically peripheral facial palsy.
Among the thirteen patients suffering from pFP as clinically diagnosed, only five (38.4%) displayed a lesion in the pons, which anatomically correlated with the side of the FP; the correlation between presence of lesion(s) in the pons and presence of pFP was significant (χ: p = 0.02). Additionally, presence of lesion(s) in the cortex (observed in 61.5% of patients with pFP) was significantly correlated with presence of pFP (p = 0.01). Finally, presence of lesion(s) in the cortex was highly correlated with presence of cFP (p = 0.02).
4. Discussion
This study analyzed the relationship between clinical features of FP and lesions location as visible on MRI in MS patients. We found that FP clinically diagnosed as pFP (13 out of 18 in our sample) occurred in MS patients who displayed demyelinating lesions not only in the pons (38.4% of cases) but also in other parts of the CNS (cortex with or without brainstem involvement). We also found that FP clinically diagnosed as cFP occurred in MS patients who displayed lesions in the cortex only; only one patient who presented with this FP type displayed demyelinating lesions just in the pons.
Interestingly, we found that presence of pFP was significantly correlated both with presence of lesions in the cortex (p = 0.01) and with presence of pontine lesions (p = 0.02). In addition, there was a correlation between presence of cFP and presence of cortical lesions (p = 0.02).
Our findings are consistent with those of previous studies. It has been demonstrated that MS-related pFP is associated with lesions in parts of the CNS (that should cause a FP clinically defined as cFP) other than the pons (
) reported that only 66.7% of MS patients with pFP had at least one lesion in the brainstem, which could have explained the symptoms, while 33.3% had a lesion in other parts of the brain and none had an involvement of the facial nerve. These results suggest that a FP that shows clinical signs of a pFP, should prompt the clinician to consider that the FP may in fact be caused by lesions located in the CNS (
These results suggest that the traditional, clinical definition of central and peripheral FP may have limitations and should be revised. Sajadi et al. (
) should be used and emphasized that additional symptoms should always be considered besides the MRI findings in order to correctly understand the oigin of FP. In MS, this method is particularly useful as FP is typically associated with a number of other symptoms, for example hearing or vestibular disorders (
Di Stadio A., Dipietro L., Ralli M., Meneghello F., Minni A., Greco A., Stabile M.R., Bernitsas E.Eur rev med pharmacol sci sudden hearing loss as an early detector of multiple sclerosis: a systematic review. 2018a;22 :4611–4624. doi: 10.26355/eurrev_201807_15520.
). On the other hand, presence of multiple symptoms can make the diagnostic process challenging especially when patients are seen for the first time. In our sample, misdiagnosis occurred in 21.7% of cases; specifically, in 5% of cases FP was attributed to stroke and in 16.7% to BP as opposed to MS. As highlighted by Saleh et al., misdiagnosis may delay treatment of the primary disease (in this case, MS) thereby increasing the risk of disability (
), which may lead the clinician to attribute the FP to a stroke as opposed to MS. Patients with FP and large MS demyelinating lesions in the facial or cochlea-vestibular nuclei may also display hearing impairment or vertigo (
Di Stadio A., Dipietro L., Ralli M., Meneghello F., Minni A., Greco A., Stabile M.R., Bernitsas E.Eur rev med pharmacol sci sudden hearing loss as an early detector of multiple sclerosis: a systematic review. 2018a;22 :4611–4624. doi: 10.26355/eurrev_201807_15520.
); this may lead the clinician to attribute the FP to a BP, which can manifest with FP and hearing impairment or dysgeusia if the tract of the facial nerve between the geniculate ganglion and the stylomastoid foramen is inflamed (
Finally, in this case-series, we found that pFP was more prevalent on the left side of the face but the demyelinating lesions were spread in the cortex or in the pons equally between sides as visible on MRI. Differently from cFP, pFP recurred (37.5%) during the observational period either on the same side of the first episode or on the contralateral side; this occurred during the relapsing phases of MS, when onset of new demyelinating lesions was also visible in the MRI. This suggests that in MS patients a pFP episode should prompt the clinician to consider the FP as a sign of relapsing MS. In addition, the presence of pFP in a young healthy patient should prompt the physician to inquire about other non-specific symptoms and include MS in the differential diagnosis of FP. In the majority of cases, FP occurred later in the disease (72.3% of patients) and most patients treated with corticosteroids completely recovered.
Overall, the results of this case series suggest that in MS patients diagnosis of FP based exclusively on clinical examination is likely to be inaccurate; MS-related FP may not be recognized especially when FP is one of the first symptoms of the demyelinating disease and presents with clinical signs typical of pFP.
Our results support the idea that pFP can be related to a lesion in the brain or in the brainstem; for example, it can be due to a central demyelination as opposed to facial nerve inflammation. Because FP responds to corticosteroid treatment regardless of its origin (MS or BP) (
), prior to prescribing corticosteroids clinicians should always consider ordering an MRI . Our results should be considered preliminary and should be validated on larger data samples.
Limitations of the study: This study has several limitations. First, due to its retrospective nature, researchers were unblinded to the patients’ MS diagnosis; also retrospective analysis of MRIs might have under-estimated the actual patient MS severity, size and/or number of MS lesions, given that corticosteroid treatment might have reduced the size and/or number of inflamed areas. Finally, all MRI images were acquired with a 1.5 Tesla MRI which might have not detected demyelinating lesions small in size.
6. Conclusions
In MS patients, pFP may be the first presentation of the disease and be misdiagnosed as BP. Treatment with corticosteroids (without performing a brain MRI) may successfully contribute to FP recovery regardless of its origin, but may interfere with MS diagnosis, masking the underlying pathology and possibly leading to misdiagnosis. This is particularly problematic in early MS as it may delay the MS diagnosis; in late MS, FP may be indicative of a reactivation of the disease with a new brain lesion. Clinicians should carefully approach the diagnosis of pFP and perform a brain and temporal bone MRI investigation before pursuing a pharmacological treatment given that pFP may be due to a central involvement rather than being a sign of peripheral facial nerve damage. Our results are consistent with those of Saleh (
Di Stadio A., Dipietro L., Ralli M., Meneghello F., Minni A., Greco A., Stabile M.R., Bernitsas E.Eur rev med pharmacol sci sudden hearing loss as an early detector of multiple sclerosis: a systematic review. 2018a;22 :4611–4624. doi: 10.26355/eurrev_201807_15520.
30445-6&id=fx1.jpg){kind=link}
30445-6&id=gr1.jpg){kind=link}
30445-6&id=gr2.jpg){kind=link}
30445-6&id=gr3.jpg){kind=link}
30445-6&id=gr4.jpg){kind=link}
30445-6&id=gr5.jpg){kind=link}