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 Table of Contents  
TEACHING IMAGES
Year : 2019  |  Volume : 7  |  Issue : 2  |  Page : 313-316

Intracranial hypertension secondary to levofloxacin-therapy


Department of Medicine, Federal University of Santa Maria, Santa Maria, RS, Brazil

Date of Submission24-Aug-2019
Date of Decision03-Sep-2019
Date of Acceptance04-Sep-2019
Date of Web Publication16-Dec-2019

Correspondence Address:
Mr. Jamir Pitton Rissardo
Department of Medicine, Federal University of Santa Maria, Santa Maria, RS
Brazil
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/amhs.amhs_118_19

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  Abstract 


Idiopathic intracranial hypertension (ICH) is characterized by elevated intracranial pressure without an evident etiology. Here, we report the case of an adult male who presented with headache, diplopia, blurred vision, and nausea. The patient stated that he had searched a general practitioner 1 week ago because he had experienced cough, dyspnea, and fever. The physician started levofloxacin. On admission, the patient reported that his respiratory symptoms recovered. However, he complained about the beginning of neurological symptoms. On neurological examination, papilledema and unilateral abducens weakness were observed. A brain magnetic resonance imaging showed radiographic features of ICH. A lumbar puncture had an opening pressure of 50 cmH2O. Levofloxacin was withdrawn, and acetazolamide 250 mg bid was started. After 2 weeks, the patient had full recovery of the symptoms, and 4 weeks later, no papilledema was observed.

Keywords: Headache, intracranial hypertension, levofloxacin, quinolones


How to cite this article:
Rissardo JP, Fornari Caprara AL. Intracranial hypertension secondary to levofloxacin-therapy. Arch Med Health Sci 2019;7:313-6

How to cite this URL:
Rissardo JP, Fornari Caprara AL. Intracranial hypertension secondary to levofloxacin-therapy. Arch Med Health Sci [serial online] 2019 [cited 2022 Jul 5];7:313-6. Available from: https://www.amhsjournal.org/text.asp?2019/7/2/313/273053




  Introduction Top


Idiopathic intracranial hypertension (ICH) (IIH) (also known as pseudotumor cerebri or benign ICH) is defined by an elevated intracranial pressure without an evident etiology. Several case studies have described the association of secondary ICH with a variety of diseases and drugs.[1] In this way, the relationship between IIH and fluoroquinolones was first described by Banzas et al. in a child using nalidixic acid.[2] After this report, many other quinolones were listed as a possible cause of pseudotumor cerebri.

Only a few cases of levofloxacin-induced pseudotumor cerebri syndrome have been reported. To the authors' knowledge, there are five case reports in literature. Nevertheless, these individuals did not present any imaging abnormality.[3],[4],[5],[6],[7] In this way, the present case is the first to describe a patient with IIH secondary to levofloxacin who developed abnormal radiological findings on a brain magnetic resonance imaging (MRI).

Herein, we report the case of an adult male who presented IIH features after starting levofloxacin.


  Illustrative Case Top


A 34-year-old male who presented with severe throbbing headache, diplopia, blurred vision, and nausea within 2 days of symptom onset was admitted to our hospital. The patient stated that he had searched a general practitioner 1 week ago because he experienced cough, dyspnea, and fever. A diagnosis of bacterial pneumonia was done. Laboratory tests and chest X-ray were not requested. The physician started levofloxacin 750 mg per oral once a day.

On admission, the patient reported that his respiratory symptoms recovered on the 3rd day after the initiation of medication. However, on the 5th day, he complained about the beginning of the neurological symptoms mentioned above. He was previously a health secretary, and his family history was negative for neurological diseases. The general examination was normal including body mass index (22.4 kg/m2).

On neurological examination, he is right handed and left abducens weakness was observed. Cranial nerve (CN) examination was remarkable for horizontal diplopia in all directions of gaze and was most prominent when focusing on distant objects especially and more so when looking toward the left. Bilateral vertical eye movements and right horizontal eye movements were intact. The pupils were symmetrical in both size and reaction to light, and there was no ptosis, nystagmus, or skew deviation. The visual acuity was 20/30 in the left eye and 20/25 in the right eye. Fundoscopy revealed bilateral moderate papilledema characterized by obscuration of some segments, circumferential halo, and elevated borders (Frisén grade 3).

A brain MRI showed radiographic features suggestive of ICH [Figure 1]. The brain MRI and an MR venography were with and without contrast (gadolinium) to rule out meningeal enhancement, cerebral venous thrombosis, hydrocephalus, mass, and structural lesions. Laboratory tests were within normal limits. A lumbar puncture had an opening pressure (OP) of 50 cmH2O. Cerebrospinal fluid (CSF) analysis showed 2.0/mm3 of white blood cell count, 20 mg/dL of protein, and 61 mg/dL of glucose (serum glucose of 94 mg/dL). The CSF culture was negative. There was immediate relief of the headache after the CSF drainage.
Figure 1: Neuroimaging demonstrating radiographic findings that support the diagnosis of idiopathic intracranial hypertension. Sagittal (a), axial T2-weighted (b), axial T1-weighted (c), and right-eye maximization T2-weighted images (d) showing features suggestive of pseudotumor cerebri. Slight protrusion of the optic nerve head (d-black arrow), flattening of the posterior sclera (d-dark gray arrow), prominent subarachnoid space around the optic nerve (d-white arrow), and vertical tortuosity of the optic nerve (d-white gray) in the right optic nerve

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Levofloxacin was withdrawn, and acetazolamide 250 mg bid was started, titrating the dose up to 1 g a day. After 1 week, the patient had full recovery of the symptoms. Four weeks later, no papilledema was observed, and acetazolamide was tapered off. The visual acuity was 20/20 in both eyes.


  Discussion Top


Fluoroquinolones and tetracyclines are the classes of antibiotics most frequently reported in association with IIH. Quinolone-induced IIH has been documented with the use of ciprofloxacin, nalidixic acid, ofloxacin, pefloxacin, and levofloxacin.[8] Sodhi et al. studied the risk of secondary pseudotumor cerebri syndrome with fluoroquinolones. Their nested case–control study showed that the risk for current users of quinolones to develop IIH is more than five times. In addition, they concluded that individuals who experience symptoms of raised intracranial pressure while taking fluoroquinolones should be advised to seek medical attention.[9]

The exact pathogenesis of IIH is unknown, and many associated etiologies were already reported. In this context, the study of lardizabal explained that probably quinolones may decrease the CSF absorption in the subarachnoid space.[3] More specifically, the regulatory components of CSF production and absorption including mitochondrial metabolites (glutamate) and endocrinologic factors (insulin and steroid hormones) are probably dysfunctional in patients with increased intracranial pressure.[10],[11] Therefore, quinolones may exert some direct control in the neuro-endocrinologic factor or in predisposed individuals, with these factors promoting an indirect increase in the intracranial pressure.

Another hypothesis for the pathophysiologic mechanism of this disorder could be the venous outflow abnormalities as cerebral venous sinus structural deformities are commonly found in patients with IIH. However, there are conflicts about if these vascular findings are a causative phenomenon or secondary to IIH.[8],[12] Third, obesity is related to increased peripheral vascular resistance, and some reports suggested by indirect means that the high body mass index may lead to increased intracranial venous pressure, and ultimately to IIH,[12],[13] and fourth, abnormalities in Vitamin A metabolism. This was presupposed based on case reports of patients intoxicated by Vitamin A, in whom the initial presentation and diagnosis was IIH. However, serum derivatives and receptor of this vitamin were elevated only in some, but not all, IIH individuals.[12],[14]

The radiographic findings are not diagnostic of IIH, nor could their absence exclude it. Many of the individual MR neuroradiologic markers lack sensitivity in the diagnosis of pseudotumor cerebri; it is always the constellation and combination of 2–3 signs in the context of a clinical picture that is crucial for the diagnosis of this pathology.[15] In this way, some MRI abnormalities are commonly associated with this disorder. The most frequent findings are related with the optic system and include flattening of the posterior sclera, empty sella turcica, distension of perioptic CSF space, vertical tortuosity of the orbital optic nerve, gadolinium enhancement, and intraocular protrusion of the prelaminar optic nerve. Another unusual feature is the transverse sinus septum causing sinus stenosis.[1]

Lim et al. assessed the value of these neuroimaging findings in children with IIH. The features evaluated were more likely to be present in the IIH group but were also found in the control group. It is worthy to mention that they demonstrated that intraocular protrusion of the prelaminar optic nerve, tortuosity of the optic nerve, and empty sella are highly specific but of low sensitivity.[15] However, in the study by Agid et al., the posterior globe flattening was the only sign that, if present, strongly suggests the diagnosis of IIH with a specificity of 100% and a sensitivity of approximately 40%.[16]

Friedman et al. in 2013 revised the diagnosis for IIH and postulated five criteria for it. The consensus guideline of Mollan et al. in 2018 supported the previous requirements, which are papilledema, normal CN examination (except abducens palsy), characteristic neuroimaging findings, elevated OP, and normal CSF analysis and culture.[13],[14] One interesting point discussed in their revision is the popularized term “IIH without papilledema” (IIHWOP) that according to them was overused and misused throughout the time. Furthermore, the majority of the patients diagnosed without papilledema probably only have chronic daily headache with a coincident elevated intracranial pressure, which does not require vigilant ophthalmic monitoring, as they tend not to develop papilledema later or even lose their vision.[14] However, once a definite IIHWOP is diagnosed, all patients should be managed as typical IIH and counseled about weight management.[13]

Only a few cases of levofloxacin-induced pseudotumor cerebri syndrome have been reported. We identified five cases after a review of the English-language literature and compared them with the present case [Table 1].[3],[4],[5],[6],[7] To the authors' knowledge, these cases described individuals without any imaging abnormality. In this way, the present case is the first to describe a patient with IIH secondary to levofloxacin who developed abnormal radiological findings on brain MRI. A literature search was performed in Embase, Google Scholar, Lilacs, Medline, SciELO, and ScienceDirect, using a set of terms that included levofloxacin, idiopathic intracranial hypertension, benign intracranial hypertension, and pseudotumor cerebri.
Table 1: Reported cases of patients who developed intracranial hypertension secondary to levofloxacin therapy

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The diagnosis of levofloxacin-induced IIH in the present study is supported by the symptoms starting days after the beginning of levofloxacin and recovery of the symptoms within weeks of the drug withdrawal. There may have been a synergistic factor that was the subject of pneumonia since Mycoplasma pneumoniae is a well-known microorganism related to HII.[7] However, in our case, the general practitioner prescribed levofloxacin without requesting a laboratory test.

Our report suggests that levofloxacin should be listed as a probable cause of secondary pseudotumor cerebri syndrome. Moreover, this case proposes similar radiologic findings between IIH induced by levofloxacin and IIH occurred without this drug. Therefore, the elevated intracranial pressure is a life-threatening condition, and physicians should inform patients about the signs and symptoms of this adverse effect.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Brodsky MC, Vaphiades M. Magnetic resonance imaging in pseudotumor cerebri. Ophthalmology 1998;105:1686-93.  Back to cited text no. 1
    
2.
Banzas TM, Clegg P, Balerio A. Intracranial hypertension during treatment with nalidixic acid. Arch Argent Pediatr 1970;68:121-6.  Back to cited text no. 2
    
3.
Lardizabal DV. Intracranial hypertension and levofloxacin: A case report. Headache 2009;49:300-1.  Back to cited text no. 3
    
4.
Cellini M, Strobbe E, Gizzi C, Campos EC. Pseudotumour cerebri syndrome and levofloxacin therapy: A case report. Neuroophthalmology 2010;34:358-60.  Back to cited text no. 4
    
5.
van der Laan LE, Schaaf HS, Solomons R, Willemse M, Mohamed N, Baboolal SO, et al. Probable levofloxacin-associated secondary intracranial hypertension in a child with multidrug-resistant tuberculosis. Pediatr Infect Dis J 2016;35:706-8.  Back to cited text no. 5
    
6.
Schettino R, Ruggiero C, Di Caprio D. Levofloxacin and intracranial hypertension in a patient with spondylodiscitis: A case report. Arch Med 2016;1:19.  Back to cited text no. 6
    
7.
Maffeis L, Dilena R, Guez S, Menni F, Bana C, Osnaghi S, et al. Pseudotumour cerebri associated with Mycoplasma pneumoniae infection and treatment with levofloxacin: A case report. BMC Pediatr 2019;19:4.  Back to cited text no. 7
    
8.
Milanlioglu A, Torlak PT. Intracranial hypertension and ciprofloxacin. Neurol India 2011;59:302-3.  Back to cited text no. 8
[PUBMED]  [Full text]  
9.
Sodhi M, Sheldon CA, Carleton B, Etminan M. Oral fluoroquinolones and risk of secondary pseudotumor cerebri syndrome: Nested case-control study. Neurology 2017;89:792-5.  Back to cited text no. 9
    
10.
Sheldon CA, Kwon YJ, Liu GT, McCormack SE. An integrated mechanism of pediatric pseudotumor cerebri syndrome: Evidence of bioenergetic and hormonal regulation of cerebrospinal fluid dynamics. Pediatr Res 2015;77:282-9.  Back to cited text no. 10
    
11.
Cao F, Chen M, Li G, Ye K, Huang X, Zheng X. Altered expression of metabotropic glutamate receptor 1 alpha after acute diffuse brain injury: Effect of the competitive antagonist 1-aminoindan-1, 5-dicarboxylic acid. Neural Regen Res 2012;7:119-24.  Back to cited text no. 11
  [Full text]  
12.
Biousse V, Bruce BB, Newman NJ. Update on the pathophysiology and management of idiopathic intracranial hypertension. J Neurol Neurosurg Psychiatry 2012;83:488-94.  Back to cited text no. 12
    
13.
Mollan SP, Davies B, Silver NC, Shaw S, Mallucci CL, Wakerley BR, et al. Idiopathic intracranial hypertension: Consensus guidelines on management. J Neurol Neurosurg Psychiatry 2018;89:1088-100.  Back to cited text no. 13
    
14.
Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology 2013;81:1159-65.  Back to cited text no. 14
    
15.
Lim MJ, Pushparajah K, Jan W, Calver D, Lin JP. Magnetic resonance imaging changes in idiopathic intracranial hypertension in children. J Child Neurol 2010;25:294-9.  Back to cited text no. 15
    
16.
Agid R, Farb RI, Willinsky RA, Mikulis DJ, Tomlinson G. Idiopathic intracranial hypertension: The validity of cross-sectional neuroimaging signs. Neuroradiology 2006;48:521-7.  Back to cited text no. 16
    


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