A Review of the Literature and a New Reportable Association: Pharyngeal-Cervical-Brachial Variant in Patient with Influenza B
- 157 Downloads
Pharyngeal-Cervical-Brachial variant is a rare diagnosis. Several clinical features are considered to be diagnostic, although ongoing work related to laboratory work-up and conduction studies are being evaluated as possible adjuncts to support in the diagnosis of this demyelinating disorder. It has been reportedly associated with many infections, bacterial or viral, but there has never been a reported association of this neurologic disorder with an Influenza B infection. We present the first case of Pharyngeal-Cervical-Brachial variant in an adult male who tested positive for Influenza B virus. We also provided a review of the literature, and highlighted the key features in the diagnosis of this interesting condition. Given this new association, a high index of suspicion for the diagnosis of Pharyngeal-Cervical-Brachial variant is indicated for patients presenting with an Influenza B infection.
KeywordsDemyelinating polyradiculoneuropathy Guillain-Barre Miller Fisher Influenza B virus Pharyngeal-Cervical-Brachial variant
Guillain-Barre Syndrome (GBS) is an autoimmune, usually postinfectious, acute, inflammatory, and demyelinating polyradiculoneuropathy. Previously reported associated infections include Campylobacter jejuni, Cytomegalovirus, Epstein-Barr virus, Influenza A, Mycoplasma pneumoniae, Haemophilus influenzae, hepatitis (A, B), and, most recently, Zika virus . Variants of GBS exist and include conditions such as Bickerstaff Brainstem encephalitis, Miller-Fisher syndrome, and Pharyngeal-Cervical-Brachial (PCB) variant. PCB is a rare condition, with a few documented cases across all ages [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12]. Patients with PCB typically present with rapidly progressive oropharyngeal and cervicobrachial weakness, as well as neck, shoulder, and swallowing dysfunction and upper limb areflexia, with the lower limbs either preserved or mildly affected. This has led to speculation by clinicians and neurologists that PCB is likely a localized subtype of GBS [2, 13, 14]. Important to note that PCB can be mimicked by other conditions, that a clinician must be able to differentiate, that include, but are not limited to, brainstem strokes, myasthenia gravis, Wernicke’s encephalopathy, rhombencephalitis, and botulism .
Based on the newest diagnostic guidelines, PCB is diagnosed by physical examination in the presence of diagnostic features . Nerve conduction studies and needle electromyography (EMG), serologic confirmation as well as an antecedent infection are supportive features, however, are not necessary for diagnosis. Electrodiagnostic studies aid in providing prognostic features, as well as in classifying the GBS variant as a demyelinating or axonal neuropathy. Antibodies that have been described in previous studies include monospecific anti-GT1a antibodies [6, 7, 16] with GQ1b reactivity, as well as IgG antibodies to GM1, GM1b, GD1a, or GalNAcGD1a  can also be diagnostic supportive tools. As in GBS, infections have been commonly associated with PCB, and include a similar list of the infections listed above. Of the viral infections, Influenza B virus has never been reported in the literature to have an association or antecedence with the development of PCB. We present a case that describes a patient with PCB variant GBS likely associated with Influenza B. In addition, we performed a review of the literature to highlight other common conditions found to be associated with the development of PCB.
A 42-year-old Caucasian male presented to an academic community hospital with complaints of dysphonia, drooling, and inability to swallow. The patient stated that 5 days prior to admission, he noted flu-like symptoms: sore throat, postnasal drip, and rhinorrhea associated with a subjective fever. His symptoms progressed with dysphagia, dysphonia, and drooling resulting in dysphagia of solids and liquids. Sick contacts at home included his wife, who also had flu-like symptoms. The patient denied prior occurrence of similar symptoms. He denied any neurological symptoms, new rashes, any animal contact, canned food or raw meat consumption, insect bites, recent immunizations, or travel. He had no known allergies. He had no known family history of neurological disorders. He was a chronic smoker and drank alcohol daily.
Upon physical examination, due to dysphonia, the patient was communicating by writing. Oral examination revealed a partially open mouth, demonstrating an oral cavity filled with saliva. Although his tongue was normal in size, the right side was fasciculating. His uvula was asymmetrical and swollen with no erythema or evidence of infection. On pulmonary examination, the patient had decreased breath sounds in the left lower lung. Neurological examination revealed an alert patient, oriented to time, place, and person. He had intact facial sensation without evidence of proptosis. Although the face was symmetric, the patient was unable to puff his cheeks, move his tongue in any direction, and was demonstrating severe dysphonia resulting in incomprehensible speech. His gag reflex was intact. He had bilateral postural tremor. He had weakness in neck flexion and proximal upper limb muscle (4/5); otherwise, his strength was 5/5 in all other extremities. His tone and sensation were normal throughout. Deep tendon reflexes were trace at the bicep muscles bilaterally, but were otherwise absent throughout. Hoffman signs were negative bilaterally. No oculomotor alterations were noted. The remainder of his neurological examination was unremarkable. His cardiovascular, abdominal, and skin examinations were unremarkable.
Blood pressure was normal. There was asymptomatic bradycardia with a heart rate as low as 40 beats per minute. He was febrile with a temperature of 102.0°F, and tachypneic with a respiratory rate of 20 breaths per minute. He had evidence of oxygen desaturation in the 80 s on pulse oximetry. His laboratory results were unremarkable except for hyperkalemia of 5.5 mmol/L. His rapid group A strep test and throat culture were negative. He tested positive for Influenza B on PCR. CT scan of the neck showed a thick, yet normal-variant uvula with no suspicion for infection or abscesses. It also showed mild asymmetric prominence of the right laryngeal ventricle without midline shift of the ipsilateral or concordant which most likely is a normal variant. An ENT was consulted for laryngoscopy which was unremarkable for any structural abnormality. MRI of the brain showed mild non-specific white matter changes, otherwise unremarkable.
Over the course of the next 6 h, the patient developed new loss of gag reflex. Neurology was consulted, and the patient was moved to the ICU to monitor his respiratory status in light of a presumed diagnosis of a demyelinating disease, suspected to be Pharyngeal-Cervical-Brachial variant of GBS. Intravenous immunoglobulin (IVIG) 0.4 gram/kg per day was initiated for a 5-day course. The patient remained nil per os: his maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and vital capacity (VC) [with a cut-off of < 1.5 L given his weight of 75 kg] were monitored every 4 h. His MIP remained > 30 cmH2O and his MEP > 40 cmH2O. His VC initially declined from 2 to 1.5 L, but then plateaued at 3 L throughout the remainder of his admission and his bradycardia resolved after IVIG was started. EMG showed markedly increased distal latency consistent with a demyelinating polyneuropathy, with mild slowing of conduction study. Three days after initiation of IVIG, the patient showed evidence of improvement in proximal muscle weakness and facial and tongue muscle function, with tongue fasciculation resolution and reflex return, including his gag reflex. His dysphonia has improved dramatically. He was able to tolerate level I pureed diets without evidence of aspiration. His pulse oximeter showed a saturation of > 95% on room air.
Materials and Methods
Based on the data collected, 35 reports, including 51 cases of PCB, were documented. Six patients had non-identifiable causes of PCB, while 24 cases were reported to have PCB associated with respiratory tract infections. Of those, organisms associated with respiratory infections in 22 of the 24 cases were not identified, whereas 1 of the 24 cases was identified as a bacterial pneumonia, unknown organism, and the other 1 of the 24 cases identified a combination of CMV and EBV infection. Thirteen of the 51 reported cases were related to gastrointestinal disease, with 7 of them associated with C. jejuni, 1 of them with CMV, and the other 5 of the 13 cases of unknown infectious cause. One of the 51 cases was thought to be a post-transfusion reaction after administration of 1 packed red blood cell unit, while another 1 case of the 51 cases was related to an acute hepatitis A infection. Vaccines were also noted to be associated with the development of PCB, with 4 total cases, each being caused by meningococcal vaccine, Dukoral vaccine, flu vaccine, and a combination of meningococcal/polio/oral typhoid vaccines. Last but not the least, 1 case of PCB was deemed associated with urinary retention and constipation.
PCB, a GBS variant, is a demyelinating polyradiculoneuropathy characterized by oropharyngeal and cervicobrachial weakness. In some situations, there might be associated neck, shoulder, and swallowing deficits with upper limb areflexia, with lower extremity preservation. We present the first reported case of PCB manifesting with Influenza B virus in an adult male.
As can be seen from Fig. 1, the majority of the reported cases are related to respiratory tract infections, with a large number of them being unspecified, possibly due to being viral in origin and out of the window of serologic and diagnostic detection by laboratory methods. The next most common cause of PCB based on our review is gastrointestinal infectious diseases, with the majority being due to C. jejuni, and the remainder either unspecified or viral CMV-caused. Other causes such as post-transfusion or post-vaccination reactions have not unheard of in other demyelinating conditions [3, 17, 18, 19, 20, 21] given that there appears to be an immunologic trigger leading to neurological disease, making an association with PCB difficult to refute. As for the association of neuropathies with constipation or urinary retention, it is unclear how there may be a relationship between these conditions, and further studies might be needed for ongoing evaluation. There have been no documented cases or prior incidences of Influenza B being detected when PCB was diagnosed. Needless to say, a causative relationship between Influenza B virus and PCB cannot be assumed in our patient, but an association can be safely illustrated given that it was the only remarkable insult that we were able to detect upon our patient’s presentation.
Diagnostic features of Pharyngeal-Cervical-Brachial variant of Guillain-Barre, adopted from Wakerley BR, Yuki N. “Pharyngeal-Cervical-Brachial variant of Guillain-Barré syndrome.” J Neurol Neurosurg Psychiatry 2014; 85:339-344
Required diagnostic features
Strongly supportive diagnostic features
Symmetric oropharyngeal weakness and neck weakness and arm weakness and arm areflexia/hyporelfexia
Antecedent infectious symptoms
Absent ataxia and disturbed consciousness and prominent leg weakness
Cerebrospinal fluid albuminocytological dissociation
Monophasic illness pattern AND interval between onset and nadir of oropharyngeal or arm weakness between 12 h and 28 days and subsequent clinical plateau
Neurophysiological evidence of neuropathy
Absence of identified alternative diagnosis
Presence of IgG anti-GT1a or anti-GQ1b antibodies
To further support our diagnosis, MRI was done and did not show any structural lesions that can mimic the patient’s presentation, and EMG was performed, with findings consistent with a demyelinating polyneuropathy, given the results of markedly increased distal latency of the motor studies and mild slowing of the conduction velocity. In addition, our patient’s symptomatic improvement in terms of neurological function was evident three days after initiation of IVIG, further supporting our diagnosis of a GBS variant. Although not acquired from our facility, further testing with serum or cerebrospinal fluid agents (such as antibodies or albuminocytological dissociation, respectively) would have been a beneficial supportive addition to our diagnosis.
PCB, already a rare diagnosis, has never been reported to be associated with Influenza B. We present the first case of PCB in an adult male who tested positive for Influenza B. Given this new finding, an index of suspicion for PCB in patients with a history of any of multiple different infections, including now influenza B, should be higher. We agree with the proposed diagnostic guidelines that mention antecedent infections as supportive of PCB. Future research is needed to determine causal links with various infections, including now Influenza B.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
- 17.Caminero A, Ahmed A. Clinical and electrodiagnostic presentation of pharyngeal-cervical-brachial variant of Guillain-Barre syndrome. Neurology. 2013;7(poster):80.Google Scholar
- 22.Wakerley BR, Kokubun N, Funakoshi K, Nagashima T, Hirata K, Yuki N. Clinical classification of 103 Japanese patients with Guillain-Barré syndrome. J Neurol Sci. 2016;269:43–7.Google Scholar
- 24.Shinoda K, Murai H, Shibata K, Samejima S, Kaneto S, Takashima N, et al. An overlap case of Fisher syndrome and pharyngeal-cervical-brachial variant of Guillain-Barré syndrome. Clin Neurol. 2012;52:30–3.Google Scholar
- 26.Barzegar M, Toopchizadeh V, Shiva S. Recurrence of childhood Guillain-Barré syndrome as a pharyngeal-cervical-brachial variant: a case report. J Pediatr Neurol. 2010:399–401.Google Scholar
- 29.Sekiguchi Y, Mori M, Misawa S, Sawai N, Yuki N, Beppu M, et al. How often and when Fisher syndrome is overlapped by Guillain-Barré syndrome or Bickerstaff brainstem encephalitis. Eur J Neurol. 2016;0:1–6.Google Scholar
- 31.Hall JN, Sheikh MN, Shumak SL. Pharyngeal-cervical-brachial variant of Guillain-Barre syndrome. J Neurol Res. 2014;4(2–3):88–90.Google Scholar
- 32.Sakai T, Kondo M, Tomimoto H, Yamagishi Y. An overlap case of Fisher syndrome and pharyngealcervical-brachial variant of Guillain-Barré syndrome associated with urinary retention and constipation. Clin Neurol. 2016;56:694–7.Google Scholar
- 34.McNicholas N, O’Dowd S, McNamara B, O’Toole O. An unusual presentation of Guillain-Barré syndrome in a young man with bilateral upper extremity weakness. BMJ Case Rep. 2015. https://doi.org/10.1136/bcr-2015-210375.