Pituitary Apoplexy 4/8/2019

Thanks Brandan for presenting an elderly lady who developed sudden onset headache, CN3 palsy, and  bitemporal hemianopia. She had a CTH that was unremarkable the day before, and a repeat CT found a large pituitary “mass,” and MRI was concerning for pituitary apoplexy!

This case demonstrates a few important concepts:


Visual Field Pathology (commonly tested!)

VF

A: Optic Nerve pathology or structural pathology leading to complete blindness in one eye, i.e. trauma, optic nerve neuropathy, optic neuritis (i.e. MS)

B: Bitemporal hemianopsia= optic chiasma pathology until proven otherwise.

C: Homonymous hemianopsia: Optic tract pathology

D: Homonymous quadrantanopsia: Optic radiation, think occipital lobe pathology


Oculomotor nerve palsy (CNIII palsy)

  • Findings: Down and out on the affected eye.
  • Physiology: Lacteral rectus, with CN VI innervation, remains intact and not opposed by the medial rectus which is innerved by CN III. Down because the superior oblique (innerved by CN IV) is unopposed by the paralyzed superior rectus, inferior rectus, and inferior oblique
  • DDx:
    • Ischemic (affects somatic fibers over parasympathetic, typically spares the pupils)
    • Inflammation,
    • Infection
    • Tumors (mass effect so both somatic and parasympathetic fibers are typically affected)
    • Demyelinating disease
    • Autoimmune
    • Cavernous sinus thrombosis (don’t miss this!)

Pituitary apoplexy: A Medical Emergency!

  • Pathophysiology:
    • Hemorrhage or infarction of the pituitary gland usually involving a pituitary adenoma, and occasionally it may be the first manifestation of a pituitary adenoma.
  • Risk factors:
    • HTN, surgeries, coagulopathies, certain meds (i.e. VKA, DOACs, antiplatelets)
  • Presentation:
    • Sudden onset headache, vomiting, encephalopathy, visual field defect, hemodynamic instability (esp with ACTH defects).
    • DI is very common in the immediate setting, but as axons in the pituitary die, ADH is released which can lead to SIADH (but only transient until stores of ADH are used up), followed by recovery but it depends on the extent of the damage.
  • Management: IVF, hydrocortisone (get labs first)
    • Acute secondary adrenal insufficiency is seen in 2/3 of pts, important cause of mortality.
      • Acute hypocortisolemia leads to hemodynamic instability
      • Inc vasopressin release from posterior pit can lead to fluid and lyte disturbances.
      • Any signs of hemodynamic instability: Can do 50-100mg hydrocortisone Q6H or continuous infusion 2-4mg/hr
    • Role of surgical management:
      • Decision to operate based on whether there is deteriorating level of consciousness, severely reduced visual acuity, or presence of visual field defects.
      • Otherwise, medical management with corticosteroids, monitoring, re-evaluation is recommended.
    • Vision outcomes: Conflicting data on medical vs surgical management.
    • Pituitary function outcomes: No difference b/w surgical vs medical management

Please refer to this paper for a detailed read on pituitary apoplexy!

Amaurosis Fugax 2/5/2019

We presented a case of a 63yo M with 30-pk-yr tobacco use, HTN, HLD, and prior CVD 7 months ago presenting with acute onset vision loss of the left eye, described as “seeing through a black mesh with spots of clear vision.” His symptom lasted for 2 hours before gradually resolving on its own. His cardiovascular and neuro exam were unremarkable, and his fundoscopic exam was normal other some mild AV nicking (a sign found with long standing hypertension). Labs and imaging including CTA did not find any acute etiology. A MR of the orbit was also done without any abnormal findings.

Ultimately pt was diagnosed with transient monocular vision loss (TMVL) most likely secondary to an episode of TIA!


Common things being more common, the most common cause of transient monocular vision loss is ischemia/vascular related!

Ischemic/Vascular Etiology

  • TIA
  • CRVO: Classic painFUL vision loss, flame hemorrhage (blood and thunder descriptor) on fundoscopic exam
    • Acute angle closure glaucoma is the most common factor predisposing to retinal retinal vein occlusion
    • Other risk factors: Sickle cell, HIV, Waldenstrom, sarcoidosis, syphilis
  • CRAO: Classic painLESS vision loss, cherry red spot with retinal pallor is a classic description
  • Carotid artery syndrome (transient retinal hypoperfusion or microemboli)

Neurology Etiology

  • Optic neuritis
  • MS
  • NMO
  • Optic nerve ischemia
  • Increased ICP

Inflammatory Etiology

  • GCA
    • Association with polymyalgia rheumatica
    • Typical patient demographics: Age > 55, F > M (2:1), Scandinavian/Northern European ancestry
    • Other associated sx: Fever, headache, jaw claudication, scalp tenderness
    • ESR and CRP typically elevated but this is NOT always the case!

Other

  • Glaucoma
  • Idiopathic
  • Smart phone use in the dark (I am not kidding), please see this article for more details

Management of TIA

In addition to treating risk factors i.e. HTN, HLD, DM2, a question often came up…

To DAPT or not DAPT?

CHANCE, a multicenter, randomized, placebo-controlled trial published in 2013 (Wang et al.) in the NEJM, revealed that DAPT within 24 hours after a TIA or mild ischemic stroke is beneficial in reducing 90-day stroke risk without an increase in bleeding complications vs aspirin monotherapy. This study was done in China with a patient population with higher incidence of undertreated modifiable risk factors and greater cerebral vascular disease burden, hence its applicability to an American patient population is unclear.

Then the POINT trial came along funded by the NIH, which saw the same benefit in DAPT after TIA/ischemic stroke but with increased bleeding risk compared to aspirin monotherapy.

Bottomline: CHANCE indicates 21 days of DAPT post TIA/ischemic stroke is helpful without increasing bleeding risk, and in POINT, 90 days of DPT is also beneficial but it increases bleeding risk. Per 2018 AHA/ASA guideline:

  • In patients presenting with minor stroke, treatment for 21 days with dual antiplatelet therapy (aspirin and clopidogrel) begun within 24 hours can be beneficial for early secondary stroke prevention for a period of up to 90 days from symptom onset.

Bilateral Panuveitis 1/31/2019

Thanks to Amran for presenting an interesting case of a 84yo M with RA on MTX & Prednisone, and an unspecified self-resolving total body rash 1 month prior to presentation, presenting with pain, redness, and vision in both eyes. Detailed fundoscopic exam was consistent with bilateral anterior granulomatous uveitis as well as retinitis, consistent with a panuveitis picture. Initial work up revealed RPR and EIA positivity, his HLA-B27 also returned positive but he has no other findings suggestive of spondylosing arthropathy. His vitreal centesis returned positive for VZV!

In Summary:

  • Tertiary syphilis without CNS/ocular involvement
  • Panuveitis secondary to VZV
  • Incidental HLA-B27 without e/o ankylosing spondylitis

Let’s start off with a basic review of the eye anatomy:

eye

The Uvea consists of the iris, ciliary body, and the choroid. Uveitis is inflammation of any of these structures.

The Standardization of Uveitis Nomenclature (SUN) Working group guidance on uveitis terminology categorizes uveitis anatomically as follows;

  • Anterior uveitis; localized primarily to the anterior segment of the eye, involving iris and pars plicata.
  • Intermediate uveitis; localized to the vitreous cavity and pars plana, presence of WBC in the vitreous.
  • Posterior uveitis; localized to the choroid and retina.
  • Panuveitis; inflammation involving anterior, intermediate and posterior uveal structure

Uveitis can be further classified into granulomatous (presence of macrophages, multinucleated giant cells) vs non-granulomatous. A granulomatous uveitis is typically more likely to be an infectious process (although can still be idiopathic or Sarcoidosis).

Etiology of Uveitis

  • Infectious:
    • HSV:
      • Usually unilateral, might have other clues such as presence of vesicles.
    • Toxoplasmosis:
      • Ocular toxoplasmosis for some reasons occurs more frequently in immunocompetent hosts.
    • Lyme Disease
    • Syphilis:
      • Accounts for less than 1% of cases of uveitis but can affect any part of the eye.
    • TB (Yes ocular TB exists!)
      • Uncommon in North America, suspect in endemic regions and worsening sx with glucocorticoids.
    • CMV:
      • Almost exclusively in immunocompromised hosts i.e. AIDS patients.
      • CD4 < 50 typically.
    • Bartonella (ocular bartonellosis) aka Cat Scratch Disease:
      • Typically unilateral, has a characteristic “macular star” on fundoscopic exam.
    • West Nile virus
    • Ebola (case reports)
    • Zika virus
    • Varicella Zoster Virus: Can affect any part of the eye
  • Non-infectious: Most common = HLA-B27 related arthropathies and reactive arthritis, tends to be unilateral and causes an anterior uveitis picture
    • Sarcoidosis
    • IBD
    • Ankylosing spondylitis
    • Relapsing polychrondritis:
    • Behcets
    • Juvenile idiopathic arthritis
    • Psoriatic arthritis
    • Reactive arthritis
    • TINU (tubulointerstitial nephritis and uveitis) syndrome
      • Uncommon, occurs in adolescent/young F, fever, myalgias, anemia, LFT elevation, chronic uveitis, interstitial nephritis.
    • MS: Optic neuritis
    • Vogt-Koyangi-Harada(VKH)Syndrome:
      • Japanese and Hispanics, bilateral panuveitis, neurological/auditory sx
    • Penetrating trauma
    • Drug-induced:
      • Rifbutin, fluoroquinolone, monoclonal ab
  • Other conditions that might mimic uveitis
    • Retinal tears
    • Ischemia
    • Leukemia
    • Lymphoma
    • Ocular melanoma
    • Pigmentary dispersion syndrome
    • Retinitis pigmentosa
    • Retinoblastoma

Management

  • Treat underlying cause
  • If viral: Anti-virals (acyclovir, valacyclovir), add on topical corticosteroids.
  • Non-infectious uveitis: Management typically with topical steroids. If posterior, some have suggested using difluprednate or periocular glucocorticoid injections. Systemic tx is reserve for pts with bilateral disease, inability to tolerate intraocular injections, or systemic conditions i.e. Behcets.
  • If refractory to steroids in non-infectious causes, can consider MTX, azathioprine, mycophenolate, cyclosporine, or tacrolimus.
  • TNF alpha inhibitors u.e. adalimumab has good evidence in the tx of non-infectious intermediate, posterior, and panuveitis. Can also be considered first line in management of Behcet.
  • Sulfasalazine has been shown in a few small studies to prevent HLA-B27 associated uveitis.

Please refer to this previous blog post for more details on tertiary syphilis!

MS vs NMO!

Thanks to Amran for presenting the case of an elderly woman with history of “transverse myelitis” 10 years ago who presented with b/l leg weakness, numbness, and tingling, found to have several spinal cord enhancements as well as optic chiasm enhacement on T2 FLAIR imaging concerning for MS vs NMO!


Clinical pearls

  • MS and NMO most commonly affect women (2:1 and 10:1 respectively).
  • To meet diagnostic criteria for MS, patients must demonstrate CNS lesions in both space and time via clinical or MRI findings.
  • NMP affects the optic nerve and spinal cord much more so than the brain/brainstem.
  • Presence of AQP4 serum antibodies are specific to NMO.
  • Treatment for acute MS flare or NMO flare involves high dose steroids or plasma exchange.
  • The most effective chronic treatment for relapsing/remitting MS is natalizumab, not effective for NMO and may even be harmful.

Framework for myelopathies:

 

capture

Demyelinating diseases that present with myelitis:

capture2

Multiple sclerosis:

Epi

  • Most commonly affects young adults
  • Mean age of onset 28-31. Though can present between 15-50
  • Affects women 2:1
  • Life expectance is reduced by ~10 years

Presentation

  • Most common symptoms
    • Sensory disturbances (90%)
      • Numbness, tingling, pins and needles
      • Lhermitte sign (flexion of the neck causes sensation of electric shock that radiates down the spine into the limbs). Can be seen in tumors, cervical disk herniation, and trauma as well.
    • Fatigue and/or sleep disturbance (85%)
      • Unrelated to amount of activity performed
      • Worsened by depression
    • Motor issues and spasticity (80%)
      • Lower extremities most commonly affected
      • Paraparesis, paraplegia
    • Cognitive impairment (70%)
      • Attention, executive function, short term memory
      • Depression (60%) likely contributes
    • Bowel or bladder dysfunction (50-75%)
    • Visual disturbance (25%)
      • Internuclear ophthalmoplegia
        • Lost adduction and horizontal nystagmus of the abducting eye
        • Lesion in the medial longitudinal fasciculus of the brainstem on the side of diminished adduction
        • Convergence is preserved
      • Optic neuritis
        • Unilateral eye pain accentuated by ocular movement
        • Variable degree of visual loss (90% regain normal vision)
  • Characteristic features
    • Different types
      • Clinically isolated syndrome (first attack)
      • Relapsing-remitting
      • Secondary progressive
      • Primary progressive
      • Progressive relapsing
    • Heat sensitivity AKA “Uhthoff phenomenon” (80%)
      • Due to slowing of neuronal conduction with increased body temperature
  • Diagnosis
    • McDonald Criteria (revised in 2017)
    • Clinical or radiographic
    • CSF studies are not indicated unless atypical presentation
  • Treatment
    • Acute episode
      • Glucocorticoids
        • Solumedrol 1 g IV x 3-5 days
      • Plasma exchange
        • If failed glucocortidoids
    • Chronic
      • Disease modifying therapy
        • Good for relapsing-remitting MS

Gradenigo Syndrome

Thanks to Amit for presenting the fascinating case of a middle-aged woman with history of DM2 who presented with subacute onset of unilateral periorbital pain, L CN 6 palsy, and L otorrhea, with MRI findings of petrous apicitis consistent with the super rare Gradenigo syndrome!


Clinical Pearls

  • Gradenigo syndrome is a rare and life threatening complication of otitis media and involves inflammation of the medial aspect of the temporal bone, specifically the apex of the petrous bone (a pyramid shaped bone jutting medially from the temporal bone)
  • Gradenigo is clinically characterized by a triad of otorrhea, diplopia (due to CN6 palsy), and hemifacial pain (CN5 palsy).
  • This is a very rare complication since most cases of otitis media are treated with antibiotics early on.
  • Remember that a common cause of an isolated CN 6 palsy in a diabetic patient is diabetic neuropathy/ophthalmoplegia.  A patient who has more cranial nerves affected than CN6 alone, you should be concerned about cavernous sinus thrombosis.

Gradenigo syndrome:

  • First described in 1904 by Guiseppe Gradenigo.

    Petrous pyramid
    Source: AO Surgery Reference
  • A rare and potentially life threatening complication of otitis media involving the inflammation of the apex of petrous pyramid (medial aspect of temporal bone). Occurs any time between 1 week to 3 months after acute otitis media (AOM) and up to 3 years after chronic suppurative otitis media (CSOM).
    • Should suspect this syndrome any time there is CN 6 palsy in the setting of otitis media, whether acute or chronic
  • Clinically, Gradenigo syndrome is characterized by triad of ear discharge, diplopia, and hemifacial pain
    • Suppurative otitis media (ear discharge and pain)
    • Trigeminal neuralgia involvement causes pain in the distribution of the nerve manifested as hemicranial headache and hemi-facial pain
    • Abducens nerve involvement causes ipsilateral lateral rectus palsy and lateral gaze palsy
  • Infection spread from suppurative otitis media to the petrous apex may be via pneumatized air cell tracts, through vascular channels, or as a result of direct extension through fascial planes
  • Organisms are not well studied but the most common one appears to be pseudomonas.  Staph, strep, pneumococcus, and TB have also been reported.
  • If left untreated, it can result in serious complications such as meningitis, intra-cranial abscess, sinus thrombosis
  • Treatment
    • Broad spectrum antibiotics IV for up to 6 weeks (to treat a presumed temporal bone osteomyelitis)
    • Fluoroquinolone ear drops
    • Tight glucose control
  • Differential diagnoses to consider:
    • Cavernous sinus thrombosis
      • Headache
      • cavernous sinus thrombosis
        Source: UpToDate

        Papilledema

      • CN palsies (see picture of what runs through cavernous sinus)
    • Ophthalmoplegic migraine:
      • Rare condition, often manifests in children and young adults
      • Diagnosis of exclusion
      • Most commonly affects CN3 (but can go to CN4 and CN6 as well)
      • Can sometimes precede the headache
      • Review article here
    • Diabetic ophthalmoplegia
      • Common cause of isolated CN6 palsy
    • Neoplasms
      • Nasopharyngeal cancer
      • Plasmacytoma
      • Pituitary adenoma
      • CN6 neuroma
      • Skull base tumors
      • Sohenoid sinus tumors
      • Squamous cell
    • Stroke
    • Demyelinating diseases
    • Vasculitis
    • Idiopathic intracranial hypertension

Complications of acute otitis media

  • Intratemporal
    • Tympanic membrane rupture (leads to hearing loss and pain relief!)
    • Labrynthitis (nausea, vomiting, tinnitus, vertigo)
    • Mastoiditis
    • CN palsies (including Gradenigo syndrome)
  • Extratemporal
    • Epidural, subdural, and brain abscesses
    • Skull base osteo
    • Otitic hydrocephalus (without meningitis or brain abscess)
    • Otitic meningitis
    • Lateral sinus thrombosis

Septic dural sinus thrombosis – 10/29/18

Thanks to Arathi for presenting the case of a middle-aged man with poorly controlled diabetes who presented with blurry vision and ear pain, found to have multiple cranial nerve palsies, diagnosed with skull base osteo, septic dural sinus thrombosis, and orbital cellulitis!


Clinical Pearls

  • Septic thrombophlebitis is venous thrombosis with inflammation in the setting of bacteremia and can impact any vein.  Most common cause of this condition in the hospitalized patient is indwelling lines and catheters.
    • Septic thrombophlebitis of the jugular vein is called Lemierre’s syndrome and is frequently preceded by pharyngitis.
  • Septic dural sinus thrombosis is extremely rare (only several hundred cases diagnosed in recent history).  The most common presenting symptom is headache.  There are three types:
    1. Cavernous sinus thrombosis
    2. Lateral (transverse) sinus thrombosis (rare)
    3. Superior sagittal sinus thrombosis (very rare)
  • Cavernous sinus thrombosis can present with CN III, IV, V1, V2, VI palsies.  Of these, CN VI is the first one to get affected.  So for patients presenting with lateral gaze palsy and headache, think cavernous sinus thrombosis!
  • The mainstay of treatment for septic dural sinus thrombosis is antibiotics.  Most common organism involved is staph aureus.
    • The role of anticoagulation is controversial.  The few retrospective studies done have shown a potential reduction in mortality/morbidity without a significant increase in risk of ICH.  Common practice currently is to start anticoagulation with heparin early on especially in patients with unilateral symptoms.

Septic dural sinus thrombosis

  • Uncommon disease with only several hundred cases reported in the antibiotic era. So you might only see one in your whole career!
  • Difficult to diagnose and often diagnosis and treatment are delayed.
  • Encompasses three basic syndromes: manifestations of each are unique
    1. Cavernous sinus thrombosis
    2. Lateral sinus thrombosis
    3. Superior sagittal sinus thrombosis
  • All three manifest as severe headaches which are often the presenting symptom.

Septic cavernous sinus thrombosis

  • Most common. Lots of trabeculae to trap bacteria.
  • Clinical manifestations
    • Headache and cranial nerve palsies should raise your suspicion!
    • Fever, periorbital edema. Pain is usually unilateral, retroorbital and frontal in nature with radiation to the occiput.
    • Diplopia
    • Altered mental status especially in older people
    • Less common: photophobia, tearing, and ptosis
  • Exam:
    • Fever
    • B/l ptosis, proptosis, chemosis, and ocular muscle paralysis but can be subtle
    • Fundoscopic exam with papilledema
    • Ophthalmoplegia
      • Lateral gaze palsy (isolated CN VI) is the first manifestation because of the location of the nerve in the cavernous sinus.
    • Loss of visual acuity from papilledema
    • Compression of optic nerve by mycotic aneurysm of the intercavernous segment of the internal carotid/ophthalmic artery can lead to blindness.
  • Labs:
    • CSF can show inflammatory cells in 75% of cases.
    • Micro
      • Staph aureus is the most common (70%) followed by strep and anaerobes.
    • Imaging:
      • CT venogram or MR venogram
    • Treatment
      • Antibiotics: IV and prolonged for at least 3 weeks b/c thrombus may prevent abx penetration
      • Anticoagulation: No prospective data. One retrospective study showed a significant reduction in mortality in patients with unilateral involvement who presented early and received heparin. A second showed no change in mortality but decreased morbidity.  No increased risk of ICH.  Based on these small studies, experts suggest heparin early on in patients with unilateral CST.  Duration of anticoagulation is at the discretion of the clinician (no data).
      • Surgery: Drainage of sinus infection if present, otherwise no benefit.
      • No role for steroids
  • Outcomes
    • Mortality is 30%
    • Infection can spread to meninges and the pituitary and morbidity can reach 50%.
    • 30% suffer serious sequelae:
      • Persistent oculomotor weakness
      • Blindness
      • Hemiparesis
      • Pituitary insufficiency

Septic lateral sinus thrombosis

  • Rare due to early treatment of otitis media. Generally results from untreated OM à mastoiditis à lateral sinus thrombosis.
  • Earache is generally the first symptom for several weeks

Septic superior sagittal sinus thrombosis

  • Extremely rare
  • Usually due to bacterial meningitis
  • Complete thrombosis is universally fatal.

Differential for cavernous sinus obstruction:

  • Infectious
    • fungal
    • TB
    • septic thrombosis
    • intra-orbital abscess
  • autoimmune/rheum
    • Tolosa-Hunt syndrome (granulomatous inflammation of the superior orbital vein and cavernous sinus)
    • Polyarteritis nodosa (Cogan syndrome)
    • sarcoid
    • IgG4 dz
    • GPA
  • malignant
    • Lymphoma
    • Nasopharyngeal tumor
  • Vascular
    • Thrombus

Skull base osteomyelitis:

  • Frequently seen in elderly patients with poorly controlled diabetes or immunocompromise
  • Most commonly a complication of malignant otitis externa.
  • Results in multiple cranial nerve palsies VII through XII due to involvement of the stylomastoid, jugular, and hypoglossal foramens.
  • Treatment requires antibiotics for at least 4-6 weeks.

Ophthalmoplegic migraine – 9/25/18

Thanks to Joe fore presenting the case of a middle aged woman with a history of migraines who presented with acute onset of painless binocular diplopia, found to have an isolated CN3 palsy concerning for ophthalmoplegic migraine after an extensive work up.


Clinical Pearls:

  • Types of diplopia:
    • Binocular diplopia refers to diplopia that is only present when both eyes are open (goes away when one eye is closed) and results from ocular misalignment.
    • Monocular diplopia refers to diplopia that is present even when one eye is closed and is more consistent with a local eye disease (globe related processes involving the cornea or the lens).
  • Approach to diplopia is similar to any neurologic deficit in which you would localize the lesion!
    • Upper motor neuron (brain)
    • Peripheral nerve (cranial nerves)
    • Neuromuscular junction
    • Muscle (extra-ocular muscles)
    • Globe (local eye disease or refractive error)
  • CN3 palsy usually presents with the eye in the “down and out” position and can also impact the levator palpebrae muscle resulting in ptosis.  These result from ischemia at the center of the nerve (secondary to diabetes/HTN).
    • In a patient with CN3 and a dilated pupil, you must rule out a PCA aneurysm!  Impingement of the CN3 by an enlarging aneurysm cuts off the parasympathetic fibers running on the outside of the nerve, resulting in a dilated pupil.  This is the only aneurysm that gives a warning sign before rupture!

Commonly tested gaze palsies:

Capture

Ophthalmoplegic migraine:

  • Rare condition, often manifests in children and young adults
  • Diagnosis of exclusion
  • Most commonly affects CN3 (but can go to CN4 and CN6 as well)
  • Can sometimes precede the headache
  • Permanent nerve damage has been reported and some believe that it is a demyelinating neuropathy (for more info, refer to this review article)