COVID-19-associated polyneuritis cranialis: Difference between revisions
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==Diagnosis== | ==Diagnosis== | ||
===Diagnostic Study of Choice=== | ===Diagnostic Study of Choice=== | ||
The diagnosis of [[Guillain-Barré syndrome|GBS]] and | The diagnosis of [[Guillain-Barré syndrome|GBS]] and MFS is confirmed by [[Nerve conduction studies]] (NCS). A decreased amplitude shows nerve conduction pathology. Although other reports mention decreased nerve conduction in PNC patients, [[COVID-19]] associated PNC report did not show NCS studies. | ||
===History and Symptoms=== | ===History and Symptoms=== | ||
*The hallmark of polyneuritis cranialis is [[bulbar]] weakness, [[facial nerve|facial]] weakness and [[ophthalmoparesis]]. | *The hallmark of polyneuritis cranialis (PNC) is [[bulbar]] weakness, [[facial nerve|facial]] weakness and [[ophthalmoparesis]]. | ||
*[[COVID-19]] associated polyneuritis cranialis is preceded by [[COVID-19]] infection symptoms such as [[diarrhea]], [[fever]] which can be low-grade, and [[ | *[[COVID-19]] associated polyneuritis cranialis is preceded by [[COVID-19]] infection symptoms such as [[diarrhea]], [[fever]] which can be low-grade, and [[ageusia]]. | ||
*[[Patient]] with polyneuritis cranialis may have the following symptoms as reported previously in literature:<ref name="pmid1318358">{{cite journal |vauthors=Polo A, Manganotti P, Zanette G, De Grandis D |title=Polyneuritis cranialis: clinical and electrophysiological findings |journal=J. Neurol. Neurosurg. Psychiatry |volume=55 |issue=5 |pages=398–400 |date=May 1992 |pmid=1318358 |pmc=489084 |doi=10.1136/jnnp.55.5.398 |url=}}</ref><ref name="pmid26019429">{{cite journal |vauthors=Kasundra GM, Bhargava AN, Bhushan B, Shubhakaran K, Sood I |title=Polyneuritis cranialis with generalized hyperreflexia as a presenting manifestation of thyrotoxicosis |journal=Ann Indian Acad Neurol |volume=18 |issue=2 |pages=240–2 |date=2015 |pmid=26019429 |pmc=4445207 |doi=10.4103/0972-2327.150625 |url=}}</ref><ref name="WakerleyYuki2015">{{cite journal|last1=Wakerley|first1=Benjamin R.|last2=Yuki|first2=Nobuhiro|title=Polyneuritis cranialis—subtype of Guillain–Barré syndrome?|journal=Nature Reviews Neurology|volume=11|issue=11|year=2015|pages=664–664|issn=1759-4758|doi=10.1038/nrneurol.2015.115}}</ref> | *[[Patient]] with polyneuritis cranialis may have the following symptoms as reported previously in literature:<ref name="pmid1318358">{{cite journal |vauthors=Polo A, Manganotti P, Zanette G, De Grandis D |title=Polyneuritis cranialis: clinical and electrophysiological findings |journal=J. Neurol. Neurosurg. Psychiatry |volume=55 |issue=5 |pages=398–400 |date=May 1992 |pmid=1318358 |pmc=489084 |doi=10.1136/jnnp.55.5.398 |url=}}</ref><ref name="pmid26019429">{{cite journal |vauthors=Kasundra GM, Bhargava AN, Bhushan B, Shubhakaran K, Sood I |title=Polyneuritis cranialis with generalized hyperreflexia as a presenting manifestation of thyrotoxicosis |journal=Ann Indian Acad Neurol |volume=18 |issue=2 |pages=240–2 |date=2015 |pmid=26019429 |pmc=4445207 |doi=10.4103/0972-2327.150625 |url=}}</ref><ref name="WakerleyYuki2015">{{cite journal|last1=Wakerley|first1=Benjamin R.|last2=Yuki|first2=Nobuhiro|title=Polyneuritis cranialis—subtype of Guillain–Barré syndrome?|journal=Nature Reviews Neurology|volume=11|issue=11|year=2015|pages=664–664|issn=1759-4758|doi=10.1038/nrneurol.2015.115}}</ref> | ||
**Unpleasant sensations in the [[tongue]] and [[oral cavity]] (may last a few days) | **Unpleasant sensations in the [[tongue]] and [[oral cavity]] (may last a few days) | ||
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===Physical Examination=== | ===Physical Examination=== | ||
*The presence of [[ophthalmoparesis]] with [[bulbar]] and [[facial nerve|facial]] weakness on physical examination is highly suggestive of polyneuritis cranialis. The disease is sometimes referred to as an oculopharyngeal variant of [[Guillain-Barré syndrome|GBS]].<ref name="pmid25712542">{{cite journal |vauthors=Wakerley BR, Yuki N |title=Polyneuritis cranialis: oculopharyngeal subtype of Guillain-Barré syndrome |journal=J. Neurol. |volume=262 |issue=9 |pages=2001–12 |date=September 2015 |pmid=25712542 |doi=10.1007/s00415-015-7678-7 |url=}}</ref> | *The presence of [[ophthalmoparesis]] with [[bulbar]] and [[facial nerve|facial]] weakness on physical examination is highly suggestive of polyneuritis cranialis (PNC). The disease is sometimes referred to as an oculopharyngeal variant of [[Guillain-Barré syndrome|GBS]].<ref name="pmid25712542">{{cite journal |vauthors=Wakerley BR, Yuki N |title=Polyneuritis cranialis: oculopharyngeal subtype of Guillain-Barré syndrome |journal=J. Neurol. |volume=262 |issue=9 |pages=2001–12 |date=September 2015 |pmid=25712542 |doi=10.1007/s00415-015-7678-7 |url=}}</ref> | ||
*According to the data from 15 polyneuritis cranialis cases asymmetric weakness with ocular signs such as [[ophthalmoplegia]], [[ptosis]], [[pupil]]lary changes and [[bulbar]] signs such as [[dysarthria]] or [[dysphagia]] have been most commonl reported. [[Facial nerve|Facial weakness]] is also seen.<ref name="WakerleyYuki2015">{{cite journal|last1=Wakerley|first1=Benjamin R.|last2=Yuki|first2=Nobuhiro|title=Polyneuritis cranialis—subtype of Guillain–Barré syndrome?|journal=Nature Reviews Neurology|volume=11|issue=11|year=2015|pages=664–664|issn=1759-4758|doi=10.1038/nrneurol.2015.115}}</ref> The patient with [[OVID-19]] associated polyneuritis cralialis has been describe to have following findings on | *According to the data from 15 polyneuritis cranialis cases asymmetric weakness with ocular signs such as [[ophthalmoplegia]], [[ptosis]], [[pupil]]lary changes and [[bulbar]] signs such as [[dysarthria]] or [[dysphagia]] have been most commonl reported. [[Facial nerve|Facial weakness]] is also seen.<ref name="WakerleyYuki2015">{{cite journal|last1=Wakerley|first1=Benjamin R.|last2=Yuki|first2=Nobuhiro|title=Polyneuritis cranialis—subtype of Guillain–Barré syndrome?|journal=Nature Reviews Neurology|volume=11|issue=11|year=2015|pages=664–664|issn=1759-4758|doi=10.1038/nrneurol.2015.115}}</ref> The patient with [[OVID-19]] associated polyneuritis cralialis has been describe to have following findings on physical exam: | ||
*On [[Central nervous system]] exam:<ref name="Gutiérrez-OrtizMéndez2020">{{cite journal|last1=Gutiérrez-Ortiz|first1=Consuelo|last2=Méndez|first2=Antonio|last3=Rodrigo-Rey|first3=Sara|last4=San Pedro-Murillo|first4=Eduardo|last5=Bermejo-Guerrero|first5=Laura|last6=Gordo-Mañas|first6=Ricardo|last7=de Aragón-Gómez|first7=Fernando|last8=Benito-León|first8=Julián|title=Miller Fisher Syndrome and polyneuritis cranialis in COVID-19|journal=Neurology|year=2020|pages=10.1212/WNL.0000000000009619|issn=0028-3878|doi=10.1212/WNL.0000000000009619}}</ref> | *On [[Central nervous system]] exam:<ref name="Gutiérrez-OrtizMéndez2020">{{cite journal|last1=Gutiérrez-Ortiz|first1=Consuelo|last2=Méndez|first2=Antonio|last3=Rodrigo-Rey|first3=Sara|last4=San Pedro-Murillo|first4=Eduardo|last5=Bermejo-Guerrero|first5=Laura|last6=Gordo-Mañas|first6=Ricardo|last7=de Aragón-Gómez|first7=Fernando|last8=Benito-León|first8=Julián|title=Miller Fisher Syndrome and polyneuritis cranialis in COVID-19|journal=Neurology|year=2020|pages=10.1212/WNL.0000000000009619|issn=0028-3878|doi=10.1212/WNL.0000000000009619}}</ref> | ||
**Patient is well oriented to place, time, and person. | **Patient is well oriented to place, time, and person. | ||
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**[[Intracranial pressure]] is roughly estimated by [[fundoscopy]] has been reported normal. | **[[Intracranial pressure]] is roughly estimated by [[fundoscopy]] has been reported normal. | ||
*On [[Peripheral nervous system]] exam: | *On [[Peripheral nervous system]] exam: | ||
**[[Cranial nerve]] (CN)-1: [[ | **[[Cranial nerve]] (CN)-1: [[Ageusia]] | ||
**CN II: [[Visual acuity]] may be decreased such as in the [[COVID-19]] associated polyneuritis cranialis patient had an acuity of 20/25 in both eyes | **CN II: [[Visual acuity]] may be decreased such as in the [[COVID-19]] associated polyneuritis cranialis patient had an acuity of 20/25 in both eyes | ||
**CN III, IV, VI: [[Ophthalmoparesis]], [[esotropia]] ([[abduction]] deficits), fixation [[nystagmus]] and [[gaze palsy]] were reported in [[COVID-19]] associated polyneuritis cranialis. [[Ptosis]] can also be present.<ref name="pmid26019429">{{cite journal |vauthors=Kasundra GM, Bhargava AN, Bhushan B, Shubhakaran K, Sood I |title=Polyneuritis cranialis with generalized hyperreflexia as a presenting manifestation of thyrotoxicosis |journal=Ann Indian Acad Neurol |volume=18 |issue=2 |pages=240–2 |date=2015 |pmid=26019429 |pmc=4445207 |doi=10.4103/0972-2327.150625 |url=}}</ref> | **CN III, IV, VI: [[Ophthalmoparesis]], [[esotropia]] ([[abduction]] deficits), fixation [[nystagmus]] and [[gaze palsy]] were reported in [[COVID-19]] associated polyneuritis cranialis. [[Ptosis]] can also be present.<ref name="pmid26019429">{{cite journal |vauthors=Kasundra GM, Bhargava AN, Bhushan B, Shubhakaran K, Sood I |title=Polyneuritis cranialis with generalized hyperreflexia as a presenting manifestation of thyrotoxicosis |journal=Ann Indian Acad Neurol |volume=18 |issue=2 |pages=240–2 |date=2015 |pmid=26019429 |pmc=4445207 |doi=10.4103/0972-2327.150625 |url=}}</ref> | ||
**CN VII: [[COVID-19|SARS CoV2]] associated | **CN V: Facial sensory deficit was not reported but has been reported in other cases.<ref name="pmid26019429">{{cite journal |vauthors=Kasundra GM, Bhargava AN, Bhushan B, Shubhakaran K, Sood I |title=Polyneuritis cranialis with generalized hyperreflexia as a presenting manifestation of thyrotoxicosis |journal=Ann Indian Acad Neurol |volume=18 |issue=2 |pages=240–2 |date=2015 |pmid=26019429 |pmc=4445207 |doi=10.4103/0972-2327.150625 |url=}}</ref> | ||
**CN VII: [[COVID-19|SARS CoV2]] associated PNC did not show [[Bell's palsy|facial palsy]] but cases with [[Bell's palsy|facial palsy]] have been reported.<ref name="pmid26019429">{{cite journal |vauthors=Kasundra GM, Bhargava AN, Bhushan B, Shubhakaran K, Sood I |title=Polyneuritis cranialis with generalized hyperreflexia as a presenting manifestation of thyrotoxicosis |journal=Ann Indian Acad Neurol |volume=18 |issue=2 |pages=240–2 |date=2015 |pmid=26019429 |pmc=4445207 |doi=10.4103/0972-2327.150625 |url=}}</ref> | |||
**CN IX: No pharyngeal movement and reflex pathology have been reported. | **CN IX: No pharyngeal movement and reflex pathology have been reported. | ||
**[[Reflex action|Reflexes]]: All [[deep tendon reflexes]] are absent. Globally, brisk reflexes suggest an abnormality of the [[Upper motor neuron|UMN]] or [[pyramidal tract]], while decreased reflexes suggest abnormality in the [[anterior horn]], [[lower motor neuron|LMN]], [[peripheral nerve]] or [[motor end plate]]. | **[[Reflex action|Reflexes]]: All [[deep tendon reflexes]] are absent. Globally, brisk reflexes suggest an abnormality of the [[Upper motor neuron|UMN]] or [[pyramidal tract]], while decreased reflexes suggest abnormality in the [[anterior horn]], [[lower motor neuron|LMN]], [[peripheral nerve]] or [[motor end plate]]. | ||
** [[Muscle]] strength (typically graded on the [[Medical Research Council (UK)|MRC]] scale I-V) | ** [[Muscle]] strength (typically graded on the [[Medical Research Council (UK)|MRC]] scale I-V) was normal. | ||
**[[Sensory system]]( fine touch, pain, temperature): Normal. | **[[Sensory system]]( fine touch, pain, temperature): Normal. | ||
**Muscle tone normal and no signs of rigidity were observed. | **Muscle tone was normal and no signs of rigidity were observed. | ||
*[[Motor system]] exam: There | *[[Motor system]] exam: There was no [[ataxia]] or [[hypersomnolence]].<ref name="Gutiérrez-OrtizMéndez2020">{{cite journal|last1=Gutiérrez-Ortiz|first1=Consuelo|last2=Méndez|first2=Antonio|last3=Rodrigo-Rey|first3=Sara|last4=San Pedro-Murillo|first4=Eduardo|last5=Bermejo-Guerrero|first5=Laura|last6=Gordo-Mañas|first6=Ricardo|last7=de Aragón-Gómez|first7=Fernando|last8=Benito-León|first8=Julián|title=Miller Fisher Syndrome and polyneuritis cranialis in COVID-19|journal=Neurology|year=2020|pages=10.1212/WNL.0000000000009619|issn=0028-3878|doi=10.1212/WNL.0000000000009619}}</ref> | ||
*[[Finger-to-nose]] test or [[heel-to-shin]] test did not show [[dysmetria]] or decomposition.<ref name="Gutiérrez-OrtizMéndez2020">{{cite journal|last1=Gutiérrez-Ortiz|first1=Consuelo|last2=Méndez|first2=Antonio|last3=Rodrigo-Rey|first3=Sara|last4=San Pedro-Murillo|first4=Eduardo|last5=Bermejo-Guerrero|first5=Laura|last6=Gordo-Mañas|first6=Ricardo|last7=de Aragón-Gómez|first7=Fernando|last8=Benito-León|first8=Julián|title=Miller Fisher Syndrome and polyneuritis cranialis in COVID-19|journal=Neurology|year=2020|pages=10.1212/WNL.0000000000009619|issn=0028-3878|doi=10.1212/WNL.0000000000009619}}</ref> | *[[Finger-to-nose]] test or [[heel-to-shin]] test did not show [[dysmetria]] or decomposition.<ref name="Gutiérrez-OrtizMéndez2020">{{cite journal|last1=Gutiérrez-Ortiz|first1=Consuelo|last2=Méndez|first2=Antonio|last3=Rodrigo-Rey|first3=Sara|last4=San Pedro-Murillo|first4=Eduardo|last5=Bermejo-Guerrero|first5=Laura|last6=Gordo-Mañas|first6=Ricardo|last7=de Aragón-Gómez|first7=Fernando|last8=Benito-León|first8=Julián|title=Miller Fisher Syndrome and polyneuritis cranialis in COVID-19|journal=Neurology|year=2020|pages=10.1212/WNL.0000000000009619|issn=0028-3878|doi=10.1212/WNL.0000000000009619}}</ref> | ||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
*A positive qualitative real-time [[oropharyngeal]] swab [[RT PCR]] [[COVID-19]] test.<ref name="Gutiérrez-OrtizMéndez2020">{{cite journal|last1=Gutiérrez-Ortiz|first1=Consuelo|last2=Méndez|first2=Antonio|last3=Rodrigo-Rey|first3=Sara|last4=San Pedro-Murillo|first4=Eduardo|last5=Bermejo-Guerrero|first5=Laura|last6=Gordo-Mañas|first6=Ricardo|last7=de Aragón-Gómez|first7=Fernando|last8=Benito-León|first8=Julián|title=Miller Fisher Syndrome and polyneuritis cranialis in COVID-19|journal=Neurology|year=2020|pages=10.1212/WNL.0000000000009619|issn=0028-3878|doi=10.1212/WNL.0000000000009619}}</ref> | *A positive qualitative real-time [[oropharyngeal]] swab [[RT PCR]] [[COVID-19]] test.<ref name="Gutiérrez-OrtizMéndez2020">{{cite journal|last1=Gutiérrez-Ortiz|first1=Consuelo|last2=Méndez|first2=Antonio|last3=Rodrigo-Rey|first3=Sara|last4=San Pedro-Murillo|first4=Eduardo|last5=Bermejo-Guerrero|first5=Laura|last6=Gordo-Mañas|first6=Ricardo|last7=de Aragón-Gómez|first7=Fernando|last8=Benito-León|first8=Julián|title=Miller Fisher Syndrome and polyneuritis cranialis _ in COVID-19|journal=Neurology|year=2020|pages=10.1212/WNL.0000000000009619|issn=0028-3878|doi=10.1212/WNL.0000000000009619}}</ref> | ||
*[[Cerebrospinal fluid]] (CSF) examination reveals:<ref name="Gutiérrez-OrtizMéndez2020">{{cite journal|last1=Gutiérrez-Ortiz|first1=Consuelo|last2=Méndez|first2=Antonio|last3=Rodrigo-Rey|first3=Sara|last4=San Pedro-Murillo|first4=Eduardo|last5=Bermejo-Guerrero|first5=Laura|last6=Gordo-Mañas|first6=Ricardo|last7=de Aragón-Gómez|first7=Fernando|last8=Benito-León|first8=Julián|title=Miller Fisher Syndrome and polyneuritis cranialis in COVID-19|journal=Neurology|year=2020|pages=10.1212/WNL.0000000000009619|issn=0028-3878|doi=10.1212/WNL.0000000000009619}}</ref><ref name="urlCerebral spinal fluid (CSF) collection: MedlinePlus Medical Encyclopedia">{{cite web |url=https://medlineplus.gov/ency/article/003428.htm |title=Cerebral spinal fluid (CSF) collection: MedlinePlus Medical Encyclopedia |format= |work= |accessdate=}}</ref> | *[[Cerebrospinal fluid]] (CSF) examination reveals:<ref name="Gutiérrez-OrtizMéndez2020">{{cite journal|last1=Gutiérrez-Ortiz|first1=Consuelo|last2=Méndez|first2=Antonio|last3=Rodrigo-Rey|first3=Sara|last4=San Pedro-Murillo|first4=Eduardo|last5=Bermejo-Guerrero|first5=Laura|last6=Gordo-Mañas|first6=Ricardo|last7=de Aragón-Gómez|first7=Fernando|last8=Benito-León|first8=Julián|title=Miller Fisher Syndrome and polyneuritis cranialis in COVID-19|journal=Neurology|year=2020|pages=10.1212/WNL.0000000000009619|issn=0028-3878|doi=10.1212/WNL.0000000000009619}}</ref><ref name="urlCerebral spinal fluid (CSF) collection: MedlinePlus Medical Encyclopedia">{{cite web |url=https://medlineplus.gov/ency/article/003428.htm |title=Cerebral spinal fluid (CSF) collection: MedlinePlus Medical Encyclopedia |format= |work= |accessdate=}}</ref> | ||
*# Opening pressure is normal (normal range 8-15 mm Hg). | *# Opening pressure is normal (normal range 8-15 mm Hg). | ||
*#[[white blood cell|WBC]] count was reported normal with all monocytes (normal range 0 - 5 WBCs all [[monocytes]]). | *#[[white blood cell|WBC]] count was reported normal with all monocytes (normal range 0 - 5 WBCs all [[monocytes]]). | ||
*#[[Cerebrospinal fluid|CSF]] protein was a little high i.e, 62 mg/dl (normal range 15 to 60 mg/dl). CSF protein can be normal as in other cases of polyneuritis cranialis due t other etiologies.<ref name="pmid26019429">{{cite journal |vauthors=Kasundra GM, Bhargava AN, Bhushan B, Shubhakaran K, Sood I |title=Polyneuritis cranialis with generalized hyperreflexia as a presenting manifestation of thyrotoxicosis |journal=Ann Indian Acad Neurol |volume=18 |issue=2 |pages=240–2 |date=2015 |pmid=26019429 |pmc=4445207 |doi=10.4103/0972-2327.150625 |url=}}</ref><ref name="TorresSalvador2019">{{cite journal|last1=Torres|first1=Alcy R|last2=Salvador|first2=Carla|last3=Mora|first3=Mauricio|last4=Mirchandani|first4=Sharam|last5=Chavez|first5=Wilson|title=Idiopathic Recurrent Polyneuritis Cranialis: A Rare Entity|journal=Cureus|year=2019|issn=2168-8184|doi=10.7759/cureus.4488}}</ref> A high CSF protein and normal cell counts can be described as ''albuminocytologic dissociation'' reported in other cases.<ref name="pmid1318358">{{cite journal |vauthors=Polo A, Manganotti P, Zanette G, De Grandis D |title=Polyneuritis cranialis: clinical and electrophysiological findings |journal=J. Neurol. Neurosurg. Psychiatry |volume=55 |issue=5 |pages=398–400 |date=May 1992 |pmid=1318358 |pmc=489084 |doi=10.1136/jnnp.55.5.398 |url=}}</ref> | *#[[Cerebrospinal fluid|CSF]] protein was a little high i.e, 62 mg/dl (normal range 15 to 60 mg/dl). CSF protein can be normal as in other cases of polyneuritis cranialis (PNC) due t other etiologies.<ref name="pmid26019429">{{cite journal |vauthors=Kasundra GM, Bhargava AN, Bhushan B, Shubhakaran K, Sood I |title=Polyneuritis cranialis with generalized hyperreflexia as a presenting manifestation of thyrotoxicosis |journal=Ann Indian Acad Neurol |volume=18 |issue=2 |pages=240–2 |date=2015 |pmid=26019429 |pmc=4445207 |doi=10.4103/0972-2327.150625 |url=}}</ref><ref name="TorresSalvador2019">{{cite journal|last1=Torres|first1=Alcy R|last2=Salvador|first2=Carla|last3=Mora|first3=Mauricio|last4=Mirchandani|first4=Sharam|last5=Chavez|first5=Wilson|title=Idiopathic Recurrent Polyneuritis Cranialis: A Rare Entity|journal=Cureus|year=2019|issn=2168-8184|doi=10.7759/cureus.4488}}</ref> A high CSF protein and normal cell counts can be described as ''albuminocytologic dissociation'' reported in other cases.<ref name="pmid1318358">{{cite journal |vauthors=Polo A, Manganotti P, Zanette G, De Grandis D |title=Polyneuritis cranialis: clinical and electrophysiological findings |journal=J. Neurol. Neurosurg. Psychiatry |volume=55 |issue=5 |pages=398–400 |date=May 1992 |pmid=1318358 |pmc=489084 |doi=10.1136/jnnp.55.5.398 |url=}}</ref> | ||
*#[[Cerebrospinal fluid|CSF]] glucose is normal (normal range 50-80 mg/dl). | *#[[Cerebrospinal fluid|CSF]] glucose is normal (normal range 50-80 mg/dl). | ||
*#[[Cerebrospinal fluid|CSF]] [[cytology]] was normal. | *#[[Cerebrospinal fluid|CSF]] [[cytology]] was normal. | ||
*# [[Cerebrospinal fluid|CSF]] cultures and [[serology]] were sterile and negative respectively. | *# [[Cerebrospinal fluid|CSF]] cultures and [[serology]] were sterile and negative respectively. | ||
*# [[Cerebrospinal fluid|CSF]] [[RT PCR]] for [[COVID-19]] was found negative in the patient. | *# [[Cerebrospinal fluid|CSF]] [[RT PCR]] for [[COVID-19]] was found negative in the patient. | ||
*Anti-ganglioside GM-1 IgM and IgG antibody levels | *Anti-ganglioside GM-1 IgM and IgG antibody levels ( antiganglioside GQ1b and GD1b) should be checked. The [[COVID-19]] associated PNC [[patient]] reported could not get the planned laboratory tests done due to hospital saturation. | ||
*[[CBC]] and differential, [[ESR]], [[CRP]], [[Basic Metabolic Panel]].<ref name="TorresSalvador2019">{{cite journal|last1=Torres|first1=Alcy R|last2=Salvador|first2=Carla|last3=Mora|first3=Mauricio|last4=Mirchandani|first4=Sharam|last5=Chavez|first5=Wilson|title=Idiopathic Recurrent Polyneuritis Cranialis: A Rare Entity|journal=Cureus|year=2019|issn=2168-8184|doi=10.7759/cureus.4488}}</ref> | *[[CBC]] and differential, [[ESR]], [[CRP]], [[Basic Metabolic Panel]], [[cardiac enzymes]] were all normal expect [[leukopenia]] was observed.<ref name="TorresSalvador2019">{{cite journal|last1=Torres|first1=Alcy R|last2=Salvador|first2=Carla|last3=Mora|first3=Mauricio|last4=Mirchandani|first4=Sharam|last5=Chavez|first5=Wilson|title=Idiopathic Recurrent Polyneuritis Cranialis: A Rare Entity|journal=Cureus|year=2019|issn=2168-8184|doi=10.7759/cureus.4488}}</ref> | ||
===Electrocardiogram=== | ===Electrocardiogram=== | ||
*There are no ECG findings associated with [[COVID-19]]-associated polyneuritis cranials. | *There are no ECG findings associated with [[COVID-19]]-associated polyneuritis cranials (PNC). | ||
*ECG shows significant findings in other manifestations or complications of [[COVID-19]] infection such as [[COVID-19-associated myocardial injury]], [[COVID-19-associated myocardial infarction]], [[COVID-19-associated arrhythmia and conduction system disease]], or [[COVID-19-associated pericarditis]]. | *ECG shows significant findings in other manifestations or complications of [[COVID-19]] infection such as [[COVID-19-associated myocardial injury]], [[COVID-19-associated myocardial infarction]], [[COVID-19-associated arrhythmia and conduction system disease]], or [[COVID-19-associated pericarditis]]. | ||
*To view the electrocardiogram findings on COVID-19, [[COVID-19 electrocardiogram|click here]]. | *To view the electrocardiogram findings on COVID-19, [[COVID-19 electrocardiogram|click here]]. | ||
===X-ray=== | ===X-ray=== | ||
*There are no x-ray findings associated with [[COVID-19]]-associated polyneuritis cranialis.<ref name="Gutiérrez-OrtizMéndez2020">{{cite journal|last1=Gutiérrez-Ortiz|first1=Consuelo|last2=Méndez|first2=Antonio|last3=Rodrigo-Rey|first3=Sara|last4=San Pedro-Murillo|first4=Eduardo|last5=Bermejo-Guerrero|first5=Laura|last6=Gordo-Mañas|first6=Ricardo|last7=de Aragón-Gómez|first7=Fernando|last8=Benito-León|first8=Julián|title=Miller Fisher Syndrome and polyneuritis cranialis in COVID-19|journal=Neurology|year=2020|pages=10.1212/WNL.0000000000009619|issn=0028-3878|doi=10.1212/WNL.0000000000009619}}</ref> | *There are no x-ray findings associated with [[COVID-19]]-associated polyneuritis cranialis (PNC).<ref name="Gutiérrez-OrtizMéndez2020">{{cite journal|last1=Gutiérrez-Ortiz|first1=Consuelo|last2=Méndez|first2=Antonio|last3=Rodrigo-Rey|first3=Sara|last4=San Pedro-Murillo|first4=Eduardo|last5=Bermejo-Guerrero|first5=Laura|last6=Gordo-Mañas|first6=Ricardo|last7=de Aragón-Gómez|first7=Fernando|last8=Benito-León|first8=Julián|title=Miller Fisher Syndrome and polyneuritis cranialis in COVID-19|journal=Neurology|year=2020|pages=10.1212/WNL.0000000000009619|issn=0028-3878|doi=10.1212/WNL.0000000000009619}}</ref> | ||
*However, an x-ray may be helpful in the diagnosis of complications of [[COVID-19]] such as [[COVID-19-associated pneumonia]] which is the most common finding associated with [[COVID-19]] infection. | *However, an x-ray may be helpful in the diagnosis of complications of [[COVID-19]] such as [[COVID-19-associated pneumonia]] which is the most common finding associated with [[COVID-19]] infection. | ||
*The x-ray finidings on [[COVID-19]] can be viewed by [[COVID-19 x ray|clicking here]]. | *The x-ray finidings on [[COVID-19]] can be viewed by [[COVID-19 x ray|clicking here]]. | ||
Line 140: | Line 139: | ||
===Other Diagnostic Studies=== | ===Other Diagnostic Studies=== | ||
There diagnostic studies associated with [[COVID-19]]-associated polyneuritis cranialis that can help in the diagnosis include: | There diagnostic studies associated with [[COVID-19]]-associated polyneuritis cranialis (PNC) that can help in the diagnosis include: | ||
*''[[Electromyography]]'': In a [[patient]] with | *''[[Electromyography]]'': In a [[patient]] with PNC the test will show no spontaneous [[skeletal muscle]] activity (and possibly neuropathic pattern) helping differentiate neurological causes from primary muscular weakness. | ||
*Lyme (B.burgdorferi) IgG, IgM EIA reflex wb (to rule out other commoner causes) | *Lyme (B.burgdorferi) IgG, IgM EIA reflex wb (to rule out other commoner causes) | ||
*TSH, T4 (rule out thyrotoxicosis especially in a patient with [[hyperthyroidism]])<ref name="pmid26019429">{{cite journal |vauthors=Kasundra GM, Bhargava AN, Bhushan B, Shubhakaran K, Sood I |title=Polyneuritis cranialis with generalized hyperreflexia as a presenting manifestation of thyrotoxicosis |journal=Ann Indian Acad Neurol |volume=18 |issue=2 |pages=240–2 |date=2015 |pmid=26019429 |pmc=4445207 |doi=10.4103/0972-2327.150625 |url=}}</ref> | *TSH, T4 (rule out thyrotoxicosis especially in a patient with [[hyperthyroidism]])<ref name="pmid26019429">{{cite journal |vauthors=Kasundra GM, Bhargava AN, Bhushan B, Shubhakaran K, Sood I |title=Polyneuritis cranialis with generalized hyperreflexia as a presenting manifestation of thyrotoxicosis |journal=Ann Indian Acad Neurol |volume=18 |issue=2 |pages=240–2 |date=2015 |pmid=26019429 |pmc=4445207 |doi=10.4103/0972-2327.150625 |url=}}</ref> |
Revision as of 17:12, 10 July 2020
COVID-19 Microchapters |
Diagnosis |
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Treatment |
Case Studies |
COVID-19-associated polyneuritis cranialis On the Web |
American Roentgen Ray Society Images of COVID-19-associated polyneuritis cranialis |
Risk calculators and risk factors for COVID-19-associated polyneuritis cranialis |
For COVID-19 frequently asked outpatient questions, click here
For COVID-19 frequently asked inpatient questions, click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Javaria Anwer M.D.[2]
Synonyms and keywords:
Overview
Polyneuritis cranialis literally means inflammation of the cranial nerves. It is a rare neurological disorder characterised by multiple cranial nerve palsies sparing the spinal cord.[1] The novel coronavirus is also emerging as a neurotropic virus. The disease is a Guillain-Barré syndrome-Miller Fisher syndrome interface. The pathogenesis of polyneuritis cranials is characterized by demyelination of lower cranial nerves. COVID-19-associated polyneuritis cranials must be differentiated from other diseases that cause bulbar weakness, facial weakness, and ophthalmoparesis.
Historical Perspective
- In 1937 French physicians Guillain G. et al. first described a postinfectious syndrome affecting the cranial nerves, associated with albuminocytological dissociation. The syndrome did not involve the limbs unlike Guillain-Barré syndrome and was called 'polyneuritis cranialis'.[2]
- The first COVID-19 outbreak news was first published by WHO on 5th January 2020.[3]
- Since mid-January 2020, right after the start of SARS-CoV2 outbreak neurological symptoms including the peripheral nervous system (PNS) symptoms have been reported in China (the first epicenter of the pandemic).[4]
- WHO declared the COVID-19 outbreak a pandemic on March 12, 2020.
- Polyneuritis cralialis associated with COVID-19 was first reported in a patient by Consuelo Gutiérrez-Ortiz et al. from Madrid, Spain on April 17th, 2020. The team reported both Miller Fisher syndrome and polyneuritis cranialis in pattients with confirmed oropharyngeal RT PCR COVID-19 test.[5]
Classification
- There is no established system for the classification of COVID-19 associated polyneuritis cranialis.
- Basis of phenotypic appearance, the disease itself is a Guillain-Barré syndrome-Miller Fisher syndrome interface.[2]
Pathophysiology
- The exact pathogenesis of COVID-19-associated polyneuritis cranials is not fully understood.
- The pathogenesis of polyneuritis cranials is characterized by demyelination of lower cranial nerves.[6] Since polyneuritis cranials lies at the interface of GBS and Miller Fisher syndrome the pathogenesis involved in Miller Fisher syndrome can help understand the dynamics.
- Novel coronavirus is usually transmitted via respiratory droplets, direct contact with infected persons, or with contaminated objects and surfaces.[7]
- The olfactory nerves are thought to be the primary site of direct viral inoculation in patients with neurological manifestations.[8] Following transmission, COVID-19's spike protein interacts with sialic acids linked to the patient's cell surface gangliosides to invade the neuron.
- The neurotropism of the novel human coronavirus is explained by the interaction between host cell proteases and Novel coronavirus's S protein spikes.[9]
- The presence of neurological symptoms in patients with severe COVID-19 disease and correlation of IL-6 with disease severity points towards the immune cause of neurological damage. novel human coronavirus being a neurotropic virus can induce a pro-inflammatory state in glial cells causing a rise in inflammatory factors such as interleukins as proved in vitro.[10][11]
- The progression to polyneuritis cranials usually involves the nerve demyelination.
- The absence of novel human coronavirus in the CSF in a patient reported, potentially clouds the possible passage through the blood-brain barrier or direct infection injury which have been included among the reasons for neurological manifestations.[11]
Causes
COVID-19-associated polyneuritis cranialis is caused after the infection with novel human coronavirus (a pan-betacoronavirus). Polyneuritis cranialis, in general, is caused by different viral or bacterial infections and in different disease states such as:
Differentiating COVID-19-associated polyneuritis cranialis from other Diseases
- COVID-19-associated polyneuritis cranials must be differentiated from other diseases that cause bulbar weakness, facial weakness, and ophthalmoparesis such as COVID-19 associated GBS, COVID-19 associated stroke.
- COVID-19 associated Guillain-Barré syndrome is characterized by ascending paralysis and loss of deep tendon reflexes. Sensory and dysautonomic symptoms are also present.[14] To better understand COVID-19-associated Guillain-Barre syndrome, click here.
- COVID-19 associated Miller Fisher Syndrome (MFS)': The presence of abnormal gait due to acute ataxic neuropathy and cervical-brachial weakness in patients with MFS can differentiate MFS with polyneuritis cranialis.[2] To better understand COVID-19-associated Miller-Fischer syndrome click here.
- COVID-19 associated stroke: A case of polyneuritis cranials presenting with slurred speech followed by difficulty in swallowing may prompt a COVID-19-associated stroke suspicion due to higher incidence. Stroke exam usually shows upper motor neuron lesion signs. The radiological proof of ischemia or hemorrhage may also be seen.[6] To better understand COVID-19-associated stroke click here
Epidemiology and Demographics
The present data is insufficient to comment on the racial, gender or age predilection of the disease. The case report for COVID-19 associated polyneuritis cranialis mentions a 39-year-old man.[5]
Risk Factors
- In general more severe patients are likely to have neurologic symptoms.[4]
- There are no established risk factors for COVID-19-associated polyneuritis cranials (PNC).
Screening
- Currently, there are no recommended guidelines in place for the routine screening for COVID-19-associated polyneuritis cranials or coronavirus disease 2019 (COVID-19). Some countries use temperature monitoring as a screening tool. Certain companies have launched the Screening Tool but there are no formal guidelines. Click here for more information on COVID-19 screening. [15]
Natural History, Complications, and Prognosis
- Most of the patients with polyneuritis cranislis present with diplopia a few days after an infection such as diarrhea or upper respiratory tract infection, in COVID-19 associated case, with diarrhea and fever. The disease develops within days.
- Prognosis is generally good. Clinical improvement usually starts within average 2 weeks in patients with polyneuritis cranislis.[6] COVID-19 associated polyneuritis cranislis has been reported to completely recover in 2 weeks.[5]
- No complications have been reported.
Diagnosis
Diagnostic Study of Choice
The diagnosis of GBS and MFS is confirmed by Nerve conduction studies (NCS). A decreased amplitude shows nerve conduction pathology. Although other reports mention decreased nerve conduction in PNC patients, COVID-19 associated PNC report did not show NCS studies.
History and Symptoms
- The hallmark of polyneuritis cranialis (PNC) is bulbar weakness, facial weakness and ophthalmoparesis.
- COVID-19 associated polyneuritis cranialis is preceded by COVID-19 infection symptoms such as diarrhea, fever which can be low-grade, and ageusia.
- Patient with polyneuritis cranialis may have the following symptoms as reported previously in literature:[6][12][2]
- Unpleasant sensations in the tongue and oral cavity (may last a few days)
- Dysphagia
- symmetrical facial or asymmetrical diplegia
- Dysarthria
- Diplopia
- Headache
Physical Examination
- The presence of ophthalmoparesis with bulbar and facial weakness on physical examination is highly suggestive of polyneuritis cranialis (PNC). The disease is sometimes referred to as an oculopharyngeal variant of GBS.[16]
- According to the data from 15 polyneuritis cranialis cases asymmetric weakness with ocular signs such as ophthalmoplegia, ptosis, pupillary changes and bulbar signs such as dysarthria or dysphagia have been most commonl reported. Facial weakness is also seen.[2] The patient with OVID-19 associated polyneuritis cralialis has been describe to have following findings on physical exam:
- On Central nervous system exam:[5]
- Patient is well oriented to place, time, and person.
- Mental status examination is normal.
- Intracranial pressure is roughly estimated by fundoscopy has been reported normal.
- On Peripheral nervous system exam:
- Cranial nerve (CN)-1: Ageusia
- CN II: Visual acuity may be decreased such as in the COVID-19 associated polyneuritis cranialis patient had an acuity of 20/25 in both eyes
- CN III, IV, VI: Ophthalmoparesis, esotropia (abduction deficits), fixation nystagmus and gaze palsy were reported in COVID-19 associated polyneuritis cranialis. Ptosis can also be present.[12]
- CN V: Facial sensory deficit was not reported but has been reported in other cases.[12]
- CN VII: SARS CoV2 associated PNC did not show facial palsy but cases with facial palsy have been reported.[12]
- CN IX: No pharyngeal movement and reflex pathology have been reported.
- Reflexes: All deep tendon reflexes are absent. Globally, brisk reflexes suggest an abnormality of the UMN or pyramidal tract, while decreased reflexes suggest abnormality in the anterior horn, LMN, peripheral nerve or motor end plate.
- Muscle strength (typically graded on the MRC scale I-V) was normal.
- Sensory system( fine touch, pain, temperature): Normal.
- Muscle tone was normal and no signs of rigidity were observed.
- Motor system exam: There was no ataxia or hypersomnolence.[5]
- Finger-to-nose test or heel-to-shin test did not show dysmetria or decomposition.[5]
Laboratory Findings
- A positive qualitative real-time oropharyngeal swab RT PCR COVID-19 test.[5]
- Cerebrospinal fluid (CSF) examination reveals:[5][17]
- Opening pressure is normal (normal range 8-15 mm Hg).
- WBC count was reported normal with all monocytes (normal range 0 - 5 WBCs all monocytes).
- CSF protein was a little high i.e, 62 mg/dl (normal range 15 to 60 mg/dl). CSF protein can be normal as in other cases of polyneuritis cranialis (PNC) due t other etiologies.[12][13] A high CSF protein and normal cell counts can be described as albuminocytologic dissociation reported in other cases.[6]
- CSF glucose is normal (normal range 50-80 mg/dl).
- CSF cytology was normal.
- CSF cultures and serology were sterile and negative respectively.
- CSF RT PCR for COVID-19 was found negative in the patient.
- Anti-ganglioside GM-1 IgM and IgG antibody levels ( antiganglioside GQ1b and GD1b) should be checked. The COVID-19 associated PNC patient reported could not get the planned laboratory tests done due to hospital saturation.
- CBC and differential, ESR, CRP, Basic Metabolic Panel, cardiac enzymes were all normal expect leukopenia was observed.[13]
Electrocardiogram
- There are no ECG findings associated with COVID-19-associated polyneuritis cranials (PNC).
- ECG shows significant findings in other manifestations or complications of COVID-19 infection such as COVID-19-associated myocardial injury, COVID-19-associated myocardial infarction, COVID-19-associated arrhythmia and conduction system disease, or COVID-19-associated pericarditis.
- To view the electrocardiogram findings on COVID-19, click here.
X-ray
- There are no x-ray findings associated with COVID-19-associated polyneuritis cranialis (PNC).[5]
- However, an x-ray may be helpful in the diagnosis of complications of COVID-19 such as COVID-19-associated pneumonia which is the most common finding associated with COVID-19 infection.
- The x-ray finidings on COVID-19 can be viewed by clicking here.
Echocardiography or Ultrasound
- There are no echocardiography/ultrasound findings associated with COVID-19-associated polyneuritis cranialis.
- However, echocardiography may be helpful in the diagnosis of cardiac complications of COVID-19 which include COVID-19-associated heart failure, or COVID-19-associated pericarditis. An abdominal ultrasound may be helpful in the case of COVID-19-associated abdominal pain.
- The echocardiographic findings on COVID-19 can be viewed by clicking here.
CT scan
- There are no CT scan findings associated with COVID-19-associated polyneuritis cranialis.[5]
- Chest CT scan may be helpful in suggesting other organ involvement in the COVID-19 which is a multi-organ disease. click here to see the CT scan findings in COVID-19.
MRI
- There are no MRI findings associated with COVID-19-associated polyneuritis cranialis.[6]
- MRI may be helpful in suggesting other organ involvement in the COVID-19 which is a multi-organ disease.
- The MRI findings in COVID-19 can be viewed by clicking here.
Other Imaging Findings
There are no other imaging findings associated with COVID-19-associated polyneuritis cranialis.
Other Diagnostic Studies
There diagnostic studies associated with COVID-19-associated polyneuritis cranialis (PNC) that can help in the diagnosis include:
- Electromyography: In a patient with PNC the test will show no spontaneous skeletal muscle activity (and possibly neuropathic pattern) helping differentiate neurological causes from primary muscular weakness.
- Lyme (B.burgdorferi) IgG, IgM EIA reflex wb (to rule out other commoner causes)
- TSH, T4 (rule out thyrotoxicosis especially in a patient with hyperthyroidism)[12]
Treatment
Medical Therapy
- The mainstay of therapy for COVID-19-associated polyneuritis cranialis is the administration of acetaminophen per oral. It can be started after the neurological symptoms develop. The treatment can be continued on the outpatient basis depending upon the patient's condition, comorbidities, and complications. Acetaminophen works primarily as an analgesic, antipyretic and may work to ameliorate inflammation. It acts by inhibiting COX enzymes and eventually decreasing prostaglandin and prostacyclin production.[18]
- COVID-19 medical therapy is as important as treating the associated polyneuritis cranialis.
- A few patients with COVID-19-associated polyneuritis cranialis may require physical therapy for residual muscle weakness.
Surgery
Surgical intervention is not recommended for the management of COVID-19-associated polyneuritis cranialis.
Primary Prevention
- The disease itself is associated with COVID-19 infection as believed to be an immune response so prevention of the infection itself is the most promising primary prevention strategy at the moment.
- There have been rigorous efforts in order to develop a vaccine for novel coronavirus and several vaccines are in the later phases of trials.[19]
- The only prevention for COVID-19 associated abdominal pain is the prevention and early diagnosis of the coronavirus-19 infection itself. According to the CDC, the measures include:[20]
- Frequent handwashing with soap and water for at least 20 seconds or using a alcohol based hand sanitizer with at least 60% alcohol.
- Staying at least 6 feet (about 2 arms’ length) from other people who do not live with you.
- Covering your mouth and nose with a cloth face cover when around others and covering sneezes and coughs.
- Cleaning and disinfecting.
References
- ↑ Pavone, Piero; Incorpora, Gemma; Romantshika, Olga; Ruggieri, Martino (2007). "Polyneuritis Cranialis: Full Recovery after Intravenous Immunoglobulins". Pediatric Neurology. 37 (3): 209–211. doi:10.1016/j.pediatrneurol.2007.05.002. ISSN 0887-8994.
- ↑ 2.0 2.1 2.2 2.3 2.4 Wakerley, Benjamin R.; Yuki, Nobuhiro (2015). "Polyneuritis cranialis—subtype of Guillain–Barré syndrome?". Nature Reviews Neurology. 11 (11): 664–664. doi:10.1038/nrneurol.2015.115. ISSN 1759-4758.
- ↑ "WHO Timeline - COVID-19".
- ↑ 4.0 4.1 Mao, Ling; Wang, Mengdie; Chen, Shanghai; He, Quanwei; Chang, Jiang; Hong, Candong; Zhou, Yifan; Wang, David; Li, Yanan; Jin, Huijuan; Hu, Bo (2020). doi:10.1101/2020.02.22.20026500. Missing or empty
|title=
(help) - ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 Gutiérrez-Ortiz, Consuelo; Méndez, Antonio; Rodrigo-Rey, Sara; San Pedro-Murillo, Eduardo; Bermejo-Guerrero, Laura; Gordo-Mañas, Ricardo; de Aragón-Gómez, Fernando; Benito-León, Julián (2020). "Miller Fisher Syndrome and polyneuritis cranialis in COVID-19". Neurology: 10.1212/WNL.0000000000009619. doi:10.1212/WNL.0000000000009619. ISSN 0028-3878.
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 Polo A, Manganotti P, Zanette G, De Grandis D (May 1992). "Polyneuritis cranialis: clinical and electrophysiological findings". J. Neurol. Neurosurg. Psychiatry. 55 (5): 398–400. doi:10.1136/jnnp.55.5.398. PMC 489084. PMID 1318358.
- ↑ "www.who.int" (PDF).
- ↑ Vavougios GD (July 2020). "Potentially irreversible olfactory and gustatory impairments in COVID-19: Indolent vs. fulminant SARS-CoV-2 neuroinfection". Brain Behav. Immun. 87: 107–108. doi:10.1016/j.bbi.2020.04.071. PMC 7185018 Check
|pmc=
value (help). PMID 32353521 Check|pmid=
value (help). - ↑ Wu Y, Xu X, Chen Z, Duan J, Hashimoto K, Yang L, Liu C, Yang C (July 2020). "Nervous system involvement after infection with COVID-19 and other coronaviruses". Brain Behav. Immun. 87: 18–22. doi:10.1016/j.bbi.2020.03.031. PMC 7146689 Check
|pmc=
value (help). PMID 32240762 Check|pmid=
value (help). - ↑ Bohmwald, Karen; Gálvez, Nicolás M. S.; Ríos, Mariana; Kalergis, Alexis M. (2018). "Neurologic Alterations Due to Respiratory Virus Infections". Frontiers in Cellular Neuroscience. 12. doi:10.3389/fncel.2018.00386. ISSN 1662-5102.
- ↑ 11.0 11.1 Bohmwald K, Gálvez N, Ríos M, Kalergis AM (2018). "Neurologic Alterations Due to Respiratory Virus Infections". Front Cell Neurosci. 12: 386. doi:10.3389/fncel.2018.00386. PMC 6212673. PMID 30416428. Vancouver style error: initials (help)
- ↑ 12.0 12.1 12.2 12.3 12.4 12.5 12.6 12.7 12.8 Kasundra GM, Bhargava AN, Bhushan B, Shubhakaran K, Sood I (2015). "Polyneuritis cranialis with generalized hyperreflexia as a presenting manifestation of thyrotoxicosis". Ann Indian Acad Neurol. 18 (2): 240–2. doi:10.4103/0972-2327.150625. PMC 4445207. PMID 26019429.
- ↑ 13.0 13.1 13.2 Torres, Alcy R; Salvador, Carla; Mora, Mauricio; Mirchandani, Sharam; Chavez, Wilson (2019). "Idiopathic Recurrent Polyneuritis Cranialis: A Rare Entity". Cureus. doi:10.7759/cureus.4488. ISSN 2168-8184.
- ↑ Willison HJ, Jacobs BC, van Doorn PA (August 2016). "Guillain-Barré syndrome". Lancet. 388 (10045): 717–27. doi:10.1016/S0140-6736(16)00339-1. PMID 26948435.
- ↑ Wakerley BR, Yuki N (September 2015). "Polyneuritis cranialis: oculopharyngeal subtype of Guillain-Barré syndrome". J. Neurol. 262 (9): 2001–12. doi:10.1007/s00415-015-7678-7. PMID 25712542.
- ↑ "Cerebral spinal fluid (CSF) collection: MedlinePlus Medical Encyclopedia".
- ↑ Capuano A, Scavone C, Racagni G, Scaglione F (July 2020). "NSAIDs in patients with viral infections, including Covid-19: Victims or perpetrators?". Pharmacol. Res. 157: 104849. doi:10.1016/j.phrs.2020.104849. PMC 7189871 Check
|pmc=
value (help). PMID 32360482 Check|pmid=
value (help). - ↑ "NIH clinical trial of investigational vaccine for COVID-19 begins | National Institutes of Health (NIH)".
- ↑ "How to Protect Yourself & Others | CDC".