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 Table of Contents  
CLINICOPATHOLOGICAL CONFERENCE
Year : 2016  |  Volume : 3  |  Issue : 1  |  Page : 65-70

Multiple cranial nerve palsies in an elderly diabetic


1 Department of Medicine, Christian Medical College, Ludhiana, Punjab, India
2 Department of Neurology, Christian Medical College, Ludhiana, Punjab, India
3 Department of ENT, Christian Medical College, Ludhiana, Punjab, India
4 Department of Radiology, Christian Medical College, Ludhiana, Punjab, India

Date of Web Publication22-Dec-2015

Correspondence Address:
Jency Maria Koshy
Department of Medicine, Christian Medical College, Ludhiana - 141 008, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2348-3334.172408

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  Abstract 

A 60-year-old man presented with multiple cranial nerve palsies on the right side. He was initiated on anti-tubercular treatment in view of lymphocytic pleocytosis on the cerebrospinal fluid study. Although he improved initially, later he worsened with cranial nerve involvement on the contralateral side. A diagnostic procedure was done, and the team reached a definitive diagnosis and patient responded to the targeted therapy.

Keywords: Base of skull osteomyelitis, diabetes mellitus, multiple cranial nerve palsy


How to cite this article:
Koshy JM, Bhalla A, Pandian J, Varghese A, George UB, Jacob JJ. Multiple cranial nerve palsies in an elderly diabetic. CHRISMED J Health Res 2016;3:65-70

How to cite this URL:
Koshy JM, Bhalla A, Pandian J, Varghese A, George UB, Jacob JJ. Multiple cranial nerve palsies in an elderly diabetic. CHRISMED J Health Res [serial online] 2016 [cited 2019 Oct 21];3:65-70. Available from: http://www.cjhr.org/text.asp?2016/3/1/65/172408


  Introduction Top


Practice of medicine still remains an art where an appropriate clinical approach and symptom based investigation can lead to a definitive diagnosis and targeted therapy. This clinicopathological case scenario reemphasize this.


  Case Summary for Discussion Top


A 60 year-old retired male employee from Rajasthan was referred to our unit. He was diagnosed to have type 2 diabetes mellitus and essential hypertension 25 years ago and was on therapy since then.

He presented for the first time to our hospital to the emergency room (ER) with diplopia and headache of 15 days duration. Headache was bilateral lasting for 30 min to 1 h that used to decrease with analgesics. There was no history of photophobia, nausea, vomiting, seizures, muscle weakness, or unsteadiness of gait. He did not have fever. He never consumed alcohol or smoke cigarettes. He was a vegetarian by diet. Twenty years ago, he had pyelonephritis with a possible drainage of pus. He had temporomandibular joint dysfunction and right mastoiditis 1 month prior to his presentation.

He was seen by the on call neurology registrar and admitted with a provisional diagnosis of isolated right 6th nerve palsy. Diabetic work up, autoimmune work up, and magnetic resonance imaging (MRI) brain were planned. Following investigations were done.

Complete blood count revealed, hemoglobin of 12.7g%, total leukocyte count of 8300/mm 3, N75, L24, E01, platelet of 4.73 L/mm 3, and erythrocyte sedimentation rate of 97 mm/h.

Biochemical reports were unremarkable with blood urea of 30 mg/dl, creatinine of 1.0 mg/dl, sodium of 138 meq/L, potassium of 3.8 meq/L, chloride of 95 meq/L, Calcium of 9.2 mg/dl, phosphorous of 4.2 mg/dl, uric acid of 6.1 mg/dl, and Hba1c of 6.5%. Liver function tests were normal.

Anti-nuclear antibody and DNA were <1.0 and 2.2 respectively (normal for the reference lab). cANCA (<0.4) and pANCA (<3.1) were also normal according to the laboratory. HBsAg, HIV and HCV antibodies were negative. Direct nasal examination (by ENT registrar) revealed bilateral pale mucosa. There were no polyps noted. Mucosal discharge was present and deviated nasal septum to the right was noted. A possibility of mucormycosis was considered.

Computed tomography (CT) head revealed right petrous apicitis, mastoiditis, mucosal thickening in the right maxillary and sphenoid sinuses. MRI brain depicted microvascular ischemic changes. Cerebrospinal fluid study (CSF) revealed nil cells, protein of 74 mg/dl and sugar of 114 mg/dl (Random blood glucose (RBS) 206 mg/dl). Potassium hydroxide (KOH) preparation, India ink, and cryptococcal antigen were negative. The patient was initiated on amoxicillin-clavulanic acid, levocetirizine and nasal drops.

Flexible endoscopic sinus surgery was done under general anesthesia. Right uncinectomy and middle meatal antrostomy was done. Right maxillary sinus was filled with fungal mucin that was cleaned and sent for histopathology and smear. Neosporin pack was applied.

KOH preparation revealed no fungal hyphae or yeast-like cells. Maxillary sinus mucus culture grew Pseudomonas and  Escherichia More Details coli which was a potential extended spectrum beta lactamase producing organism. Histopathology revealed chronic maxillary sinusitis. He was initiated on piperacillin tazobactum and injection amikacin. He was also given T. Losartan, T. Amlong AT, T. Rosuvastatin, T. piracetam/citacholine, T. Valproate C R 200 mg and insulin. After 7 days, he was discharged on cap amoxicillin-clavulanic acid with other chronic medications.

On the first follow–up, he told the neurologist that he had a 25% decrease in headache. He was given another course of antibiotics and treated with ciprofloxacin for 1 week.

One month later, he presented again to the ER with pain over the right side of the face and retro-orbital area. He had a facial deviation to the left side. He also complained of decreased hearing on the right side. There was no ear discharge or fever. His gag was impaired. Neck rigidity was not present. The autonomic system was normal. A possibility of cerebellopontine (CP) angle tumor was considered, and the patient was readmitted by the neurology registrar.

Repeat MRI brain revealed residual changes over the petromastoid area with soft tissue extending into internal auditory canal cavity with impingement of VII and VIII nerve and pachymeningeal thickening. Second CSF study revealed red blood cell of 40/mm 3 and WBC of 20/mm 3, all of which were lymphocytes. Protein was 89 mg/dl and sugar was 74 mg/dl. Anti-tuberculous treatment (ATT) was initiated with injection streptomycin/rifampicin/isoniazid/ethambutol/pyrazinamide and pyridoxine. T. Prednisolone was also started at 40 mg OD.

He had an episode of vomiting in the hospital for which anti-emetics were given. He had one episode of hypoglycemia while in the hospital. He was discharged from the hospital on ATT and steroids. He followed up in the out-patient department where he complained of intermittent episodes of headache. He also had episodes of vomiting that was thought off as rifampicin induced. Liver function test done was normal. Subsequently, vomiting subsided. Two months into ATT he continued to have morning headaches for which T. Diamox 250 mg bd was added.

ENT checkup was done and was told that pain is unlikely to be rhinogenic or otogenic origin. The patient had an episode of accelerated hypertension with blood pressure of 200/100 mm of Hg. T. Prednisolone was tapered off and stopped. Two months later the patient had worsening of deafness. Injection streptomycin (STM) and T. Diamox were also stopped. Eye movements were normal, and facial palsy had recovered. He was continued on ATT.

One month after stopping injection STM he developed B/L decreased hearing. Audiometry was reported as B/L mixed sensory hearing loss R>L. One month later, he developed B/L lateral rectus palsy along with 9th and 10th nerve palsy. At this point, the patient was referred to our unit. A diagnostic test was performed. Appropriate treatment was instituted and patient's condition improved.

Dr. Anumeha (PG Resident in Internal Medicine) was given the case to discuss:

She approached it as a case of multiple cranial nerve palsies involving 6th, 7th, 8th, 9th, and 10th cranial nerves. She further went on to various etiologies of multiple cranial nerve palsies [Table 1].[1],[2] She also discussed the various cranial nerve group syndromes [1],[2] described at the various anatomical location [Table 2].
Table 1: Various etiologies of multiple cranial nerve palsies

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Table 2: Various cranial nerve group syndromes

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Rhino cerebral mucormycosis, neurosarcoidosis, CP angle tumor, tubercular meningitis, and amyloidosis were the certain conditions she emphasized with certain features favoring these. However, none of these conditions could explain the entire temporal profile of this patient.

The case was left for open discussion. Most of the postgraduate students suggested a possibility of neurosarcoidosis and Wegner's granulomatosis. The professors also seconded this opinion. One of the postgraduate students considered a possibility of nasopharyngeal carcinoma considering a high incidence of that in Rajasthan. Another registrar suggested a possibility of base of skull osteomyelitis.


  Discussion of the Case Top


(Dr. Jency Koshy, Associate Professor of Medicine).

I approached this case as a syndrome of multiple cranial nerve palsies preceded by right ear mastoiditis in a patient with diabetes mellitus. The next question to be asked would be where the anatomical lesion is and what the etiologies are.

The highest level for multiple cranial nerve palsies would be in the brain stem. It is usually associated with long tract signs along with multiple cranial nerve palsies or gaze palsies. Focal brainstem lesions are often crossed syndromes. This patient never had any long tract signs.

The anatomy of the base of skull gives clarity to how various cranial nerves exit the cranium and where all they come together in groups that can cause certain syndromes. Let us look at various syndromes associated with multiple cranial nerve involvement. This was discussed in detail by Dr. Anumeha.

Cavernous sinus syndrome: Cavernous sinus extends from superior orbital fissure to the apex of the petrous temporal bone. This patient's nerve involvement could not be explained by this, since 3rd, 4th and 5th cranial nerves were not involved, and he had lower cranial nerve involvement.

Superior orbital fissure syndrome cannot explain the lower cranial nerve involvement.

Initial presentation of the patient was like that of petrous apex syndrome or Gradenigo's syndrome that is usually due to suppurative otitis media affecting the petrous apex of the temporal bone. In this patient, it was preceded by right mastoiditis.

CP angle lesions: Though most of the cranial nerve involvement could be explained, there was no cerebellar involvement. Most common etiology at this site would be a mass lesion. However, it would be highly unlikely with the unilateral finding in the beginning with some clinical improvement prior to the involvement of the contralateral side.

Lower cranial nerves were involved in this case implicating the extension of the inciting process to the skull base.

Looking back at this case, this patient had a mastoiditis followed by petrous apex syndrome represented by 6th nerve palsy. A month later, he had pain over the trigeminal area followed by 7th, 8th, 9th and 10th nerve palsies suggesting an extension of the disease process to the skull base causing jugular foramen syndrome.

Now that we localized the disease let us look at the various etiologies for multiple cranial neuropathies that include chronic meningitis, inflammatory diseases, neoplasms, extra medullary vascular disorders, bone disorders, trauma, etc.[2]

Chronic meningitis

Chronic meningitis is a possibility in this case. Though the initial CSF study was acellular, there was elevation of proteins. Further CSF study revealed lymphocytic pleocytosis with an elevation of proteins, suggesting meningeal inflammation. However, bacterial, fungal, and neoplastic studies were negative. Since the fungal ball was noted in maxillary sinus, one would always consider mucormycosis. This diagnosis was not further entertained since the cultures were negative for fungal and if left untreated it would have been fatal. In India, one would consider starting anti-tubercular treatment in this situation, as was done in this case.

Inflammatory and granulomatous diseases

Inflammatory and granulomatous diseases should always be considered. Isolated neurosarcoid can present with multiple cranial nerve palsies. This patient's angiotensin converting enzyme levels and Calcium levels were normal. Sinusitis would always draw one's attention to Wegner's granulomatosis. Negative Vasculitic work up and autoimmune studies discount the above possibility.

Neoplastic activity

Neoplastic meningitis and neoplasms affecting clivus/skull bone could have had a similar presentation. Though this disease was progressive, resolution of initial symptoms would obviate this possibility.

Bone disorders like paget would have been picked up on radiographic studies. Besides his alkaline phosphatase levels was normal.

Since the incidence of tuberculosis (TB) is high in India, neurologist considered a possibility of central nervous system TB and started him on anti-tubercular drugs along with steroids that were later tapered off and stopped. He initially improved transiently later showing deterioration.

After reviewing the case once again, the vascultic study was confirmed negative. A repeat MRI Brain scan was done in view of worsening of symptoms. MRI revealed that some of the previous changes had resolved with new pachymeningeal thickening along the posterior aspect of left petromastoid air cells. Changes that was initially over the right petrous bone was noted on the left side along with soft tissue in the base of skull, preclival, and retropharyngeal space.

It was decided that a histopathological diagnosis would only guide further treatment.

Dr. Ashish Varghese, Professor of ENT reviewed the scan and commented that biopsy of the soft tissue in the retropharyngeal space can be done via a pharyngeal approach.

Special care was taken to collect the tissue both in formalin and saline and was sent for histopathological and culture studies. Histopathology revealed lymphoid follicles and there was no evidence of dysplasia or vasculitis. Staphaureus was cultured from the tissue.

Dr. Uttam, Professor of Radiology was asked to review the serial scans to look at the temporal profile.

The initial MRI brain of this patient demonstrated finding mostly localized to the right petrous apex and the adjacent portions of the clivus. Very minimal adjacent soft tissue involvement in the region was noted. The follow-up scan actually seemed reassuring with some decrease noted in the MRI findings. Unfortunately, the following MRI showed an additional finding of pachymeningeal thickening along the posterior aspect of the petrous bone and in the internal auditory canal. In the imaging that followed, even though this finding resolved, there was further disease progression with bilateral petromastoid air cells showing mucosal thickening and retained secretion in the left ear. The left petrous bone was also involved by now. To make matters worse, there was now extensive soft tissue edema and inflammatory change in the adjacent carotid space extending across the midline. This had, in fact, occluded the left internal carotid artery that was now not seen on the 3D TOF angiography. It was concluded that this disease started in the right mastoid and progressed across the midline crossing over to the other side involving the left petrous bone [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6].
Figure 1: T2 flair images demonstrating hyper intensities in the region of the right petrous apex and the clivus. Fluid in the right petro mastoid air cells and middle ear are also noted. (March)

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Figure 2: The follow-up magnetic resonance imaging study a month later showing mild interval reduction in the extent of disease with involvement of the petrous bone and clivus. (April)

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Figure 3: Magnetic resonance images depicting reduction in the osseous with pachymeningeal thickening along the posterior margin of the petrous bone extending into the internal auditory canal. (April)

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Figure 4: Further follow-up study in November showing persistent secretions in the right petro mastoid air cells along with involvement of left petro mastoid air cells and the left middle ear

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Figure 5: 3D TOF angiography image from the follow-up magnetic resonance imaging of November showing soft tissue thickening along the bilateral carotid spaces extending across the midline. The left internal carotid artery is not visualized

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Figure 6: Imaging depicting meningeal thickening on the left side with resolution on the right side

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Final diagnosis

A final diagnosis of base of skull osteomyelitis manifesting as petrous apex syndrome going on to jugular foramen syndrome caused by Staphylococcus aureus was made.

Treatment

He was initiated on targeted therapy with injection cefazolin 1 G Q8 h for 2 weeks followed by cephalexin 500 mg Q6 h. One month later his cranial nerve palsy subsided except for 8th nerve palsy.

Base of skull osteomyelitis

Osteomyelitis at the base of skull was first described by Meltzer and Kelemen in 1959.[3] It is a relatively uncommon but potentially life-threatening infection that classically presents as a complication of severe external otitis, middle ear, mastoid, or sinus infection.[4] It usually occurs in diabetics and elderly as was in this case.[4]

The diagnostic criteria are a skull base infection in patients with localizing symptoms/signs at presentation with radiological or scintigraphic features indicative of bone erosion and or infection and isolation and or visualization of the pathogen from the bone or surrounding tissue.[5]

It can spread to skull base causing multiple cranial nerve palsies as was in this case. Intracranial invasion can present as meningitis, intracranial abscess, or septic thrombosis of the sigmoid sinus or internal jugular vein. It can extend extracranially causing prevertebral or para-pharyngeal abscess.

The most common etiology is a bacterial infection.  Pseudomonas aeruginosa Scientific Name Search  the most widely noted bacterial infection followed by S. aureus infection.[4] If an empirical treatment is planned it should be targeted against Pseudomonas infection.

These patients present with deep otalgia that is severe, unremitting, and throbbing. It may be accompanied by headache and temporomandibular joint pain. It is usually worse at night and is refractory to analgesics. The pain in this patient was typical. Fever is uncommon. Other diagnostic modalities are 99 Tc methylene diphosphonate (MDP) scan that reveal increased osteoblastic activity.[6] It remains positive for several months after clinical resolution. This patient had increased osteoblastic activity on 99 Tc MDP scan. Single photon emission CT are more sensitive. Gallium 67 identifies active infection and returns to normal immediately after infection.[7]


  Conclusion Top


Osteomyelitis at the base of skull is most often secondary to an infectious process. Headache, with cranial nerve deficits, should raise the suspicion of osteomyelitis at the base of skull. A thorough history and physical examination, nasopharyngeal biopsy with culture, MRI Brain, and a gallium bone scan can secure the proper diagnosis. This can be achieved only by a multidisciplinary approach. Antibiotics are effective in treating osteomyelitis and serve as the mainstay of treatment.

Acknowledgment

All the faculty of the Department of Medicine to take part in the CPC discussion. We acknowledge the Departments of Pathology and Microbiology for the diagnostic facilities offered.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Beal MF. Multiple cranial-nerve palsies: A diagnostic challenge. N Engl J Med 1990;322:461-3.  Back to cited text no. 1
[PUBMED]    
2.
Carroll CG, Campbell WW. Multiple cranial neuropathies. Semin Neurol 2009;29:53-65.  Back to cited text no. 2
    
3.
Meltzer PE, Keleman G. Pyocutaneous osteomyelitis of the temporal bone, mandible, and zygoma. Laryngoscope 1959;69:1300-16.  Back to cited text no. 3
    
4.
Chandler JR, Grobman L, Quencer R, Serafini A. Osteomyelitis of the base of the skull. Laryngoscope 1986;96:245-51.  Back to cited text no. 4
[PUBMED]    
5.
Blyth CC, Gomes L, Sorrell TC, da Cruz M, Sud A, Chen SC. Skull-base osteomyelitis: Fungal vs. bacterial infection. Clin Microbiol Infect 2011;17:306-11.  Back to cited text no. 5
    
6.
Seabold JE, Simonson TM, Weber PC, Thompson BH, Harris KG, Rezai K, et al. Cranial osteomyelitis: Diagnosis and follow-up with In-111 white blood cell and Tc-99m methylene diphosphonate bone SPECT, CT, and MR imaging. Radiology 1995;196:779-88.  Back to cited text no. 6
    
7.
Grobman LR, Ganz W, Casiano R, Goldberg S. Atypical osteomyelitis of the skull base. Laryngoscope 1989;99 (7 Pt 1):671-6.  Back to cited text no. 7
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2]



 

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