Pseudotumor Cerebri Syndrome Complicated by Diffuse Ophthalmoparesis and Polyradiculopathy

Abstract

Pseudotumor cerebri syndrome (PTCS), also known as idiopathic intracranial hypertension (IIH), is defined by elevated intracranial pressure in the absence of a structural or cerebrospinal fluid (CSF) abnormality. Typical features include headache, visual symptoms, and pulsatile tinnitus. Cranial nerve deficits are seen in a minority of cases, most often sixth nerve palsies. We present a unique cause of PTCS complicated by diffuse ophthalmoparesis and polyradiculopathy. A 27-year-old healthy woman presented with 2 weeks of blurry vision, diplopia, and facial and arm weakness. On examination, she had decreased visual acuity, markedly constricted visual fields in both eyes, with severe bilateral optic disc edema on fundus examination. There was diffuse ophthalmoparesis, right upper and lower facial weakness, and bilateral arm weakness. Magnetic resonance imaging brain revealed optic disc protrusion and a partially empty sella but no other abnormalities. Electromyogram (EMG) was consistent with bilateral C5-6 radiculopathies. Lumbar puncture revealed an opening pressure of 56 cm H2O with otherwise normal CSF constituents. She was treated with high-dose acetazolamide and methylprednisolone followed by optic nerve sheath fenestration. Due to progressive vision loss, she ultimately required ventriculoperitoneal shunting, after which her papilledema, ophthalmoparesis, and facial and arm weakness rapidly improved. This is a unique case of PTCS associated with diffuse ophthalmoparesis and polyradiculopathy. This constellation of abnormalities usually suggests an underlying inflammatory process in the subarachnoid space. However, once this has been excluded, the possibility of PTCS should be considered as early treatment can result in rapid reversal of symptoms and preserve visual function.

Introduction

Pseudotumor cerebri syndrome (PTCS), also known as idiopathic intracranial hypertension (IIH), is defined by elevated intracranial pressure in the absence of a structural, parenchymal, or cerebrospinal fluid (CSF) abnormality and absence of focal neurologic deficit with the exception of cranial neuropathy.¹ Visual loss is a feared complication and is caused by optic disc swelling.² Sixth nerve palsies are seen in a minority of cases, but involvement of multiple cranial or peripheral nerves usually indicates an alternative diagnosis. We present an unusual case of fulminant PTCS with cranial polyneuropathy (manifesting as diffuse ophthalmoparesis and facial palsy) complicated by a concomitant polyradiculopathy.

Case

An obese 27-year-old woman without significant medical history presented to the emergency room with 2 weeks of progressive blurry vision, diplopia, right facial weakness, and bilateral arm weakness. This was preceded by 2 weeks of right-sided neck and shoulder pain with associated right arm weakness. She denied headache, recent trauma, nausea, or vomiting.

On examination, she was alert with normal vitals. Visual acuity was 20/60 in the right eye and 20/40 in the left eye. She saw 4/8 Ishihara color plates with the right eye and 7/8 with the left eye. Visual fields were diffusely constricted to confrontation in both eyes. There was a right afferent pupillary defect. Ocular motility was diffusely decreased with prominent bilateral adduction deficits (pseudointernuclear ophthalmoplegia; Figure 1). Dilated fundus examination revealed severe (Frisen grade 4-5) bilateral papilledema (Figure 2). There was right upper and lower facial weakness and weakness of the bilateral deltoids (4/5), left biceps (3/5), and bilateral triceps (4/5). Sensation to pinprick was decreased in the left palm, and the left biceps reflex was decreased compared to the right.

Figure 1.

Prominent bilateral adduction deficits (pseudointernuclear ophthalmoplegia).

Figure 2.

Dilated fundus examination notable for severe bilateral papilledema.

Brain magnetic resonance imaging (MRI) showed optic disc protrusion, posterior scleral flattening (Figure 3), and a partially empty sella. Magnetic resonance venography and spinal MRI were unremarkable. Lumbar puncture revealed an opening pressure of 56 cm H2O but otherwise normal CSF studies (WBC 1/µL, RBC 1/L, protein 21 mg/dL, glucose 107 mg/dL, negative cryptococcal antigen, negative culture). Serum laboratory studies were normal: complete blood count, RPR, HIV, tuberculosis interferon gamma release assay, GQ1b, Lyme, rheumatoid factor, angiotensin-converting enzyme, antinuclear antibodies, antineutrophil cytoplasmic antibodies, C3/C4; CSF HSV and VZV PCR and West Nile virus antibodies were negative. Sensory and motor nerve conduction studies were normal. Needle EMG demonstrated mild fibrillations and positive sharp waves in the left deltoid and biceps and increased firing rate with reduced recruitment in the bilateral deltoid and left triceps consistent with bilateral C5-6 radiculopathies.

Figure 3.

Axial T2 MRI brain notable for optic disc protrusion and posterior scleral flattening. MRI indicates magnetic resonance imaging.

Due to the severity of her papilledema and vision loss, treatment with high dose acetazolamide (1000 mg 3 times daily) and intravenous methylprednisolone (1000 mg daily for total of 7 days) was initiated. Nevertheless, her symptoms worsened, prompting right optic nerve sheath fenestration. Within 48 hours, she experienced further dyschromatopsia of the left eye and nearly complete depression on automated perimetry. An external ventricular drain was therefore placed with rapid improvement in ocular motility and visual fields. This was converted to a ventriculoperitoneal shunt, and she was discharged on an acetazolamide taper. At a 3-month follow-up visit, her visual acuity was 20/25 in the right eye and 20/20 in the left eye. Visual fields were full to confrontation with a mild superior defect on automated perimetry in the right eye. There was a trace right afferent pupillary defect. Ocular motility and alignment were normal. Fundus examination revealed mild bilateral optic disc pallor. Face, arm, and leg strength and sensation were normal.

Discussion

Diagnostic criteria for PTCS require a normal neurologic examination except for cranial nerve abnormalities.¹ While sixth nerve palsies are most frequently recognized, other cranial neuropathies including facial palsy have been described, albeit in isolation.³ The mechanism by which cranial neuropathies occur in IIH is not completely understood, though is hypothesized to be secondary to pressure exerting traction forces on cranial nerves.³ There are rare reports of ophthalmoparesis in PTCS patients with high opening pressure, which resolved after shunting.⁴ In this case, the presence of cervical polyradiculopathy limits the definitive diagnosis of PTCS according to standard criteria and suggested a possible concomitant condition.

The constellation of cranial polyneuropathy, polyradiculopathy, and elevated intracranial pressure initially suggested an infiltrative or inflammatory process localizing to the subarachnoid space. Examples of such processes include infection (ie, meningitis), demyelinating disease (ie, Miller Fisher syndrome), malignancy (ie, carcinomatous meningitis), and inflammatory disease (ie, neurosarcoidosis). Optic disc edema in such cases is caused by obstruction of the arachnoid granulations (resulting in hydrocephalus and elevated intracranial pressure) or direct optic nerve infiltration, neither of which was present in this case. In the disorders previously mentioned, the CSF profile is also typically abnormal. In our case, the absence of radiographic or CSF abnormalities and the rapid resolution of all symptoms with the normalization of opening pressure was suggestive of IIH as the primary underlying cause.

Meningitis must initially be considered in the setting of papilledema and cranial nerve palsies given risk of mortality with delayed antibiotic treatment. The diagnostic criteria for PTCS requires that the CSF composition be normal with no leukocytosis or evidence of infection.¹ Given that our patient’s CSF composition was within normal limits, meningitis was excluded early in the clinical course.

Demyelinating diseases such as acute inflammatory demyelinating polyradiculopathy (AIDP) and its clinical variant Miller Fisher syndrome must also be considered in patients with oculomotor, facial, and extremity weakness.⁵ Patients with Miller Fisher syndrome classically present with the triad of ophthalmoplegia followed by areflexia and ataxia. Rare cases AIDP and Miller Fisher syndrome have been reported where in addition to the typical findings patients also have papilledema.^6,7 The CSF in patients with Miller Fisher syndrome is usually notable for albuminocytologic dissociation and antibodies against GQ1b.⁵ Our patient, however, had preserved reflexes without appreciable ataxia and no such CSF abnormalities making this diagnosis unlikely.

Carcinomatous meningitis can present with a variety of neurologic symptoms including headache, altered mental status, papilledema, cranial neuropathies, and radiculopathy.⁸ These findings are secondary to invasion of the leptomeninges by both solid and hematologic malignancies. Unlike our patient, these patients typically have findings on brain MRI indicative of malignancy including leptomeningeal and cranial nerve contrast enhancement. Cerebrospinal fluid evaluation with cytology and cytometry are also useful to aid in the diagnosis.

Inflammatory diseases such as sarcoidosis can affect the central nervous system in rare cases leading to a myriad of neurologic signs/symptoms including headache, papilledema, cranial neuropathies, peripheral neuropathy, and radiculopathy if there is involvement of the spinal cord.⁹ As noted with the abovementioned entities that cause similar symptoms, neurosarcoidosis typically has an abnormal CSF profile. These patients tend to have a lymphocytic pleocytosis with elevated protein with some having evidence of hypoglycorrachia and infrequently have elevated opening pressure. Magnetic resonance imaging of the brain may show both parenchymal and leptomeningeal lesions though patients with milder disease may initially have a normal MRI. In our case, the patient’s MRI findings had no such lesions and her CSF profile was bland aside from an elevated opening pressure making this diagnosis less likely.

Radiculopathy has been reported as a falsely localizing sign in severe PTCS, presumably due to displacement or compression of nerve roots from high intracranial pressure.^10,11 There are case reports of patients with IIH and sensory changes in the lumbosacral distribution secondary to perineural cysts. Their symptoms resolved with drainage of the cysts suggesting that the elevated intracranial pressure caused the cysts to expand and ultimately cause symptoms. It is possible that cervical perineural cysts could cause a radiculopathy, however, our patient did not have such findings on spinal cord imaging.¹² Additionally, the cysts usually take months to develop and thus we may have not seen them in such an acute presentation of PTCS in our case.

A Pubmed search of “pseudotumor cerebri syndrome” and “radiculopathy” yielded 8 results. Of these, 4 cases had a combination of radiculopathy, ophthalmoparesis, papilledema, and an elevated opening pressure concerning for pseudotumor cerebri syndrome. Of the cases, only 2 patients were ultimately diagnosed with PTCS, one of whom was a pediatric patient.^11,13 There are notable limitations in these cases and radiculopathy in suspected PTCS is often associated with other clinical features thus alternative diagnoses for elevated intracranial pressure should be considered. Similar to our patient though, the patients in these cases had improvement in symptoms with interventions to lower the intracranial pressure suggesting that elevated pressure was a primary driver of symptoms. Reports of ophthalmoparesis in PTCS are typically not accompanied by radiculopathy, but reports of radiculopathy have been sometimes accompanied by ophthalmoparesis.^4,11 Thus, there may be a progression of disease severity where one may initially demonstrate typical features of PTCS followed by ophthalmoparesis and in the most extreme cases radiculopathy. While thorough workup was unrevealing, it is possible that a second diagnosis, such as a steroid responsive disorder, was also present. However, the steroid course was very brief (7 days) and the rapid improvement in symptomatology of our patient with measures to decrease intracranial pressure (acetazolamide and ventriculoperitoneal shunting) with an otherwise negative work-up is suggestive of PTCS as the diagnosis. Fortunately, prompt recognition of papilledema led to early and aggressive vision-preserving treatment.

Conclusion

This case of papilledema with diffuse ophthalmoparesis in an adult patient highlights an unusual presentation of severe PTCS complicated by cervical radiculopathy and illustrates the importance of early recognition of papilledema to prevent permanent vision loss.