Neurology

Pseudotumor Cerebri

 

Introduction

Pseudotumor Cerebri, also known as Idiopathic Intracranial Hypertension (IIH) is a disorder of increased intracranial pressure without evidence of an underlying cause (infection, space-occupying lesion, vascular abnormality, or hydrocephalus)

 

Epidemiology

  • ​Occurs in 1 out of every 100,000 people in the general population
  • Characteristically diagnosed in obese women of childbearing age (risk is 2-20 times higher in this group)
  • Can be found in any age group (although IIH is uncommon in infants and very rare in neonates)

Major complications

  • Headaches and loss of vision
                        

Risk Factors          

  • Obesity
  • Strong correlation with IIH in women of childbearing age and post-pubescent adolescents
  • Less of an association with IIH in pre-pubescent children (perhaps a different mechanism)
  • Rapid weight gain has been associated with recurrences in patients with prior diagnosis and treatment of IIH
  • Female gender
  • Medications
    • Tetracyclines (minocycline, doxycycline)
    • Growth hormone
    • Excess vitamin A or vitamin A derivatives such as Acutane for acne
    • Oral contraceptives
  • While secondary causes of IIH are not often found in adults, a potential underlying condition is identified in 53-77% of pediatric cases.
          
    • Thyroid disease: Cases of IIH have been reported following therapy for hypothyroidism with levothyroxine
      • Most cases occurred after dose was increased due to persistently elevated TSH levels
      • Thyroxine is a regulator of sodium transport that may alter CSF dynamics
    • Corticosteroid withdrawal in pediatric patients with IBD
      • Mechanism unknown
    • Addison’s Disease
                        
      • Mechanism unknown, but it has been hypothesized that increased levels of vasopressin in these patients may cause increased cerebral volume leading to elevated ICP
    • Growth hormone therapy
      • In one large study, occurrence of IIH was 100X greater in group treated with growth hormone vs. general population
      • Proposed mechanism: GH crosses blood-brain barrier to increase local levels of IGF-1 which increases CSF production from choroid plexus
      • Usually resolves with cessation of GH therapy (can resume at a lower dose as risk of IIH appears to be dose-dependent)
      • Conditions such as obesity, Turner syndrome, chronic renal failure, Prader-Willi, and delayed puberty may increase the risk of IIH in this setting

 

Pathophysiology

  • Exact mechanism remains unclear
  • Most hypotheses are centered around:
    • Increased CSF production
    • Decreased CSF reabsorption via arachnoid granulations
    • Increased cerebral water content
      • Research regarding the role of aquaporin 4 channels regulating cerebral water content is ongoing
    • Increased cerebral venous pressure
                         
      • Possibly secondary to transverse sinus stenosis (cause/effect relationship with IIH and stenosis is unclear)

 

Clinical Presentation

  • Presenting symptoms: headache, tinnitus, visual changes (blurred vision, visual loss, photophobia)
  • Patients may also present with other signs of increased ICP: vomiting, altered behavior, decreased level of consciousness, macrocephaly
  • Headache is the main complaint among children (62-91% of cases)
  • However, some children may not complain of headache (too young to articulate or not having headaches)
    • Young patients with IIH who are not experiencing headaches tend to have more neurologic and visual signs at presentation and have a worse prognosis
    • Headache may be warning sign of elevated ICP and impending visual loss
                              
  • Physical Exam
                
    • Loss of visual acuity is seen in 6-20% of pediatric cases at presentation
    • Visual field loss is seen in up to 91% of cases
    • Papilledema on fundoscopic exam
    • Cranial nerve palsies (CN VI is most common, although III, VII, IX, and XII have also been reported)

 

Differential Diagnosis

  • Intracranial space-occupying lesion (tumor, abscess)
  • Increased CSF production (i.e. choroid plexus papilloma)
  • Decreased CSF absorption (i.e. arachnoid granulation adhesions after bacterial or other infectious meningitis, subarachnoid hemorrhage)
  • Obstructive hydrocephalus
  • Obstruction of venous outflow (i.e. venous sinus thrombosis, jugular vein compression, neck surgery)

 

Diagnosis

The Modified Dandy Criteria for Intracranial Hypertension is the official criteria used to diagnose IIH.

  • Modified Dandy Criteria
    • Signs and symptoms of increased ICP (headaches, nausea, vomiting, transient visual obscurations, papilledema)
    • No localizing focal neurological signs except unilateral/bilateral CN VI palsies
    • CSF opening pressure ≥ 250 mm H2O* but without cytological or chemical abnormalities
      • *The number of 250 mm of water is not an absolute cut-off, especially in children in whom CSF opening pressures as high as 280 mm of water have been documented to be normal
    • MRI of the brain, often with additional sequences (CT or MR venography) to exclude cerebral venous thrombosis.

 

  • Normal neurologic imaging must be demonstrated before doing diagnostic/therapeutic lumbar puncture
                              
    • Conditions with meningeal irritation and cerebral venous sinus thrombosis (CVST) can mimic pediatric IIH and may not be found on CT
    • Thus, MRI/MRV with and without gadolinium enhancement are the imaging modalities of choice
    • Some cases of IIH have characteristic imaging findings (see below)
      • Flattening of the posterior poles of the eyes (see single arrow in first image below).
      • Dilation and tortuosity of optic nerve sheaths (see triple arrows in first image below).
      • Empty sella turcica (see arrow in bottom left picture)
      • Stenosis of one/both transverse sinuses (see arrows in bottom right picture)

 

Lumbar puncture is performed after appropriate neuroimaging
         

  • Critical to measure opening pressure and rule out meningitis as cause of symptoms
    • Adults: Upper limit of normal for opening pressure is 200 mm H2O
      • Some believe this may be slightly higher in obese patients (250 mm H2O)
      • >250 mm H2O is considered abnormal
      • Between 200-250 mm H2O is considered equivocal and must decide based on rest of clinical picture
    • Children: Upper limit of normal is 250 mm H2O (280 mm in obese children)
      • > 280 mm H2O is considered abnormal
      • Values between 200-280 mm should be evaluated along with clinical evidence

 

Treatment

Treatment of IIH has two major goals:

  • The alleviation of symptoms (usually headache)
  • The preservation of vision

 

To achieve this, treatment modalities include:

  • A low-sodium weight reduction program is recommended for all obese patients with IIH as it appears to alleviate symptoms when done in conjunction with other interventions for IIH.
  • Repeated LP’s are discouraged long term as hey are painful, poorly tolerated in children and short-term in their effects (drained CSF is regenerated in one day).
    • However, LP's are recognized as a temporizing measure as a prelude to surgery or in patients who are pregnant who wish to avoid medical therapy.
  • Medications
    • Most cases resolve with medication management
    • Acetazolamide (carbonic anhydrase inhibitor) is a first-line agent as it reduces CSF production however it's dosage is sometimes limited by its side-effects
      • Dose: 25 mg/kg/day in 2-3 divided doses up to a maximum dose of 100 mg/kg or 2 gm per day until headache, disc swelling, and visual field problems resolve (typically 3-9 months)
      • Side effects: GI complaints, paresthesias, electrolyte imbalance (hyper or hypoglycemia, hypokalemia, hyponatremia, metabolic acidosis), confusion, convulsions, hematologic abnormalities.
    • Topiramate (second-line, has mild carbonic anhydrase activity)
    • In acute situations with severe visual loss, IV methylprednisolone (15 mg/kg) can be given along with acetazolamide if surgery is not immediately available
    • Other agents such as nortryptiline and valproate must be considered carefully as these have side effect of weight gain
  • Surgery
    • Optic Nerve Sheath Fenestration (ONSF) is used in cases of acute severe visual loss secondary to elevated ICP and in cases refractory to medical management
      • An incision is made in optic nerve sheath that allows CSF to drain and relieves pressure on optic nerves
      • ¾ of patients experience resolution of visual abnormalities
      • About ½ of patients with unilateral ONSF experience resolution of bilateral visual symptoms (mechanism is unclear)
    • CSF shunting
                     
      • For children with intractable headaches, vision loss, and papilledema that does not respond to ONSF
      • 90% experience improvement of symptoms with lumboperitoneal (LP) shunting
      • Complications includes infection, shunt obstruction, tonsilar herniation, and lumbar radiculopathy

 

Outcomes

Patients require regular follow-up visits until their vision and symptoms stabilize.  Intervals are dependent on the severity and duration of symtoms, as well as their response to treatment, but should be at least monthly.

Each visit should include a corrected visual acuity, formal visual field testing, and dilated fundus exam with disc photographs.

Most pediatric cases of IIH resolve within 4.7 months of therapy, however up to 10% have permanent loss of visual acuity.  In general, recurrence rate ranges from 6-22%, so vigilance is required.

 

References

 

  1. Grant L. Ko M. Pediatric Idiopathic Intracranial Hypertension (Pseudotumor Cerebri). Hormone Research in Pediatrics 2010
  2. Biousse V. Bruce B. and Newman J. Update on the Pathophysiology and Management of Idiopathic Intracranial Hypertension. J Neurol Neurosurg Psychiatry 2012
  3. Bernard T.J. et al. Chapter 25. Neurologic & Muscular Disorders. CURRENT Diagnosis & Treatment: Pediatrics.   Jan 2013