Acoustic neuroma, Menieres disease, neurofibromatosis

Question 1

What are acoustic neuromas?

Answer 1

benign tumours of the Schwann cells surrounding the auditory nerve (vestibulocochlear nerve) that innervates the inner ear

Also called vestibular schwannomas as they originate from Schwann cells

Question 2

Where are schwann cells found?

Answer 2

found in the peripheral nervous system and provide the myelin sheath around neurones.

Question 3

Where do acoustic neuromas occur?

Answer 3

They occur at the cerebellopontine angle and are sometimes referred to as cerebellopontine angle tumours.

Question 4

Where are lesions found in acoustic neuromas

Answer 4

lesions are usually located in the internal auditory canal or the cerebellopontine angle causing compression of the vestibular nerve and resulting eventually in deafness. Early diagnosis - and thus a high index of suspicion - is strongly influential to the prognosis (2)
continuous growth of the neuroma may compress the brain stem and also increase intercranial pressure

Question 5

22nd chromosome and acoustic neuromas

Answer 5

in about 40% of patients a defect in the long arm of the 22nd chromosome has been detected (1)

Question 6

Are acoustic neuromas usually unilateral or bilateral?

Answer 6

Unilateral

Question 7

What are bilateral acoustic neuromas associated?

Answer 7

Neurofibromatosis type II

Question 8

Presentation/ S + S of acoustic neuroma

Answer 8

The typical patient is aged 40-60 years presenting with a gradual onset of:

Unilateral sensorineural hearing loss (often the first symptom)
Unilateral tinnitus
Dizziness or imbalance
A sensation of fullness in the ear

They can also be associated with a facial nerve palsy if the tumour grows large enough to compress the facial nerve.

Forehead not spared

Question 9

Clinical features of acoustic neuromas

Answer 9

occipital pain on the side of the tumour

VIII nerve damage
about 90% of patients presents with unilateral sensorineural deafness developing gradually over a period of months or years
around 5% will have sudden hearing loss
vertigo which may be quite mild and tinnitus (around 70%) are common (1)
caloric paresis may be demonstrable.
V nerve damage - depression of corneal reflex occurs early. Facial pain, paraesthesia and numbness develop (1) .

VII nerve damage - facial weakness is unusual.(1)

IX, X, XI nerve damage - rare; presents as dysphagia, change in voice, palatal weakness.

compression effects of large tumours:
on cerebellum - ataxia, loss of co-ordination on ipsilateral side, nystagmus
on pons - contralateral hemiparesis
on aqueduct and 4th ventricle - raised intracranial pressure, e.g. headache (1)

Question 10

Investigations for Acoustic neuroma?

Answer 10

neuro-otological:
pure tone audiometry - demonstrates unilateral sensorineural hearing loss
brainstem audiometry - to distinguish cochlear deafness from retrocochlear disease
o speech discrimination test (1)
caloric test - expect depressed or absent response

CT - need contrast since acoustic neuromas are often isodense:
intravenous iodinated water soluble contrast (1)
metrizemide contrast into the basal cisterns or intrathecal air run up to the cerebellopontine angle clearly identifies small acoustic neuromas

MRI - especially for small intracanalicular tumours. With gadolinium - DTPA enhancement, this test is very sensitive and may demonstrate lesions of 1-2 mm in diameter within the auditory canal
T2-weighted images
contrast enhanced T1-weighted images - the sensitivity is increased by the gadolinium-based contrast medium and it can demonstrate small neuromas and intralbyrinthine lesions (2)

Question 11

Management for acoustic neuroma

Answer 11

this may involve an ENT surgeon and a neurosurgeon.

Treatment options include conservative management, gamma-knife (GK) radiosurgery, and microsurgery:

conservative management - due to the risk of interventions, small asymptomatic tumors may be managed by a “watch, wait and rescan” approach. This is more suitable in elderly patients with co morbid diseases
stereotactic radiosurgery (GK radiosurgery) - it is used in the treatment of
small to medium sized tumors
incompletely resected tumors
microsurgery - is useful in treating large acoustic neuromas. three surgical methods are used in approaching the CP angle
retrosigmoid approach
translabyrinthine approach
middle fossa approach (1)

Question 12

Systematic review of the three options

Answer 12

onservative management over a 3.1 year period showed that 51% of acoustic neuromas showed a tumour growth, 20% of acoustic neuromas ultimately required surgical intervention, and a third of the patients lost useful hearing
GK radiosurgery significantly reduced the percentage of acoustic neuromas that enlarged, to 8%, and reduced the percentage that underwent microsurgery to 4.6% over a 3.8 year period
microsurgery removed 96% of acoustic neuromas totally, with tumour recurrence, mortality, and major disability rates of 1.8%, 0.63%, and 2.9%, respectively
the study authors concluded that the majority of acoustic neuromas grow slowly, but ultimately require intervention. The authors concluded, based on the systematic review, that microsurgery provided the best tumour control, although mortality and morbidity were not completely eliminated

Question 13

What is the definition of neurofibromatosis?

Answer 13

genetic condition that causes nerve tumours (neuromas) to develop throughout the nervous system. These tumours are benign but can cause neurological and structural problems.

Question 14

Which is the more common neurofibromatosis gene - 1 or 2?

Answer 14

Neurofibromatosis type 1 is more common than neurofibromatosis type 2.

Question 15

Epidemiology of NF1

Answer 15

Neurofibromatosis occurs in approximately 1 per 3000 births. Roughly half of cases have affected relatives. All races are affected with males having a slightly higher incidence than females.

Question 16

Pathophysiology of neurofibromatosis type 1?

Answer 16

The neurofibromatosis type 1 gene is found on chromosome 17. It codes for a protein called neurofibromin, which is a tumour suppressor protein. Mutations in this gene are inherited in an autosomal dominant pattern.

Question 17

Features of neurofibromatosis Type 1 Gene (CRABBING)

Answer 17

C – Café-au-lait spots (more than 15mm diameter is significant in adults)
R – Relative with NF1
A – Axillary or inguinal freckling
BB – Bony dysplasia, such as Bowing of a long bone or sphenoid wing dysplasia
I – Iris hamartomas (Lisch nodules), which are yellow-brown spots on the iris
N – Neurofibromas
G – Glioma of the optic pathway

Question 18

NF 1 in children 0-16

Answer 18

Neurofibromas
Scoliosis
Eyes
Ataxia
Seizures
headaches
Visual disturbances
Short stature
Speech difficulties
Late puberty
ADHD,ADD,ASD

Question 19

NF Type adults 16+

Answer 19

Plexiform or subcutaneous neurofibromas
Social isolation
Depression
Headaches, seixures, nerve pain
Visual and gait disturbances
BP - if high BP consider renovascular lesions or phaeocromocytoma
Newly symptomatic optic pathway tumours - uncommon in adults
Women - increased risk of developing breast cancer

Question 20

What are neurofibromas?

Answer 20

Neurofibromas may be seen on the skin. They are skin-coloured, raised nodules or papules with a smooth, regular surface. A single skin neurofibroma without other features does not indicate neurofibromatosis. Two or more are significant

Question 21

What is a plexiform neurofibroma?

Answer 21

A plexiform neurofibroma is a larger, irregular, complex neurofibroma containing multiple cell types. A single plexiform neurofibroma is significant.

Question 22

Management of neurofibromatosis

Answer 22

Diagnosis is based on the diagnostic criteria. Genetic testing can be helpful.

There is no treatment for the underlying disease process. Management involves monitoring, managing symptoms and treating complications.
Positive family history and X-ray demonstration of bone cysts help diagnosis where cutaneous manifestations are less obvious, as in central neurofibromatosis and younger children. Evidence of precocious puberty, signs of involvement of cranial nerves - acoustic neuroma or optic glioma - and/or spinal nerves, centrally or peripherally, may also be sought.

Question 23

Complications of neurofibromatosis

Answer 23

Migraines
Epilepsy
Renal artery stenosis, causing hypertension
Learning disability
Behavioural problems (e.g., ADHD)
Scoliosis of the spine
Vision loss (secondary to optic nerve gliomas)
Malignant peripheral nerve sheath tumours
Gastrointestinal stromal tumour (a type of sarcoma)
Brain tumours
Spinal cord tumours with associated neurology (e.g., paraplegia)
Increased risk of cancer (e.g., breast cancer and leukaemia)

Question 24

The 2 unique complications worth remembering for NF1

Answer 24

The two unique complications worth remembering for NF1 are malignant peripheral nerve sheath (MPNST) and gastrointestinal stromal tumours (GIST).

Question 25

Pathophysiology of neurofibromatosis type 2?

Answer 25

gene is found on chromosome 22. It codes for a protein called merlin, a tumour suppressor protein important in Schwann cells. Schwann cells provide the myelin sheath that surrounds neurones of the peripheral nervous system. Mutations in this gene lead to schwannomas (benign tumours of the Schwann cells). Inheritance is also autosomal dominant.

Question 26

What is neurofibromatosis type 2 associated with?

Answer 26

Neurofibromatosis type 2 is particularly associated with acoustic neuromas, which are tumours of the auditory nerve that innervates the inner ear.

Surgery can be used to resect the tumours, although there is a risk of permanent nerve damage.

TOM TIP: An exam patient with bilateral acoustic neuromas almost certainly has neurofibromatosis type 2.

Question 27

What does tumours are NF2 involved in?

Answer 27

NF2 involves tumours of the vestibular branch of the eighth cranial nerve, namely vestibular schwannomas.

Question 28

What are the associated issues of NF2?

Answer 28

billateral vestibular schwannomas (VS) are emblematic of NF2, but schwannomas may form on other cranial, spinal, and peripheral nerves
central nervous system meningiomas and ependymomas, peripheral neuropathy, amyotrophy, retinal hamartomas, and subcapsular lens opacities are part of the NF2 disease spectrum (1,2, 3).

Question 29

Prevalence of NF2

Answer 29

NF2 is an inherited tumour suppressor disease with a prevalence of 1 in 60,000 and a birth incidence of 1 in 25-30,000 individuals (1)

Question 30

Associated conditions with NF 1

Answer 30

renal artery stenosis
pulmonary fibrosis
cardiomyopathy
phaeochromocytoma
optic nerve glioma
glioblastomas
ependymomas
astrocytomas
meningiomas
medullary thyroid carcinoma

Question 31

Prognosis of NF 1

Answer 31

malignant peripheral nerve sheath tumours (MPNST) (1,2)
MPNST is the term now used to refer to malignant schwannomas, neurogenic sarcomas, malignant neurilemomas, neurofibrosarcomas and spindle cell sarcomas
approximately 50% of MPNSTs are associated with NF-1 and are often due to malignant transformation of neurofibromas
NF1 patients show an 8–13% lifetime risk of developing MPNSTs (1)
MPNSTs in NF1 usually arise within a preexisting plexiform neurofibroma (PNF)
MPNSTs in NF-1 have a male predilection and occur approximately a decade earlier than in the general population.
central nervous system tumours
Fertility may be reduced, especially in males.

Up to 75% of affected individuals may have no complications.

Question 32

Diagnosis definitions of NF2 - look at GP notebook

Question 33

Clinical features of type 2 NF stemming predominantly central lesions

Answer 33

bilateral acoustic neurofibromas
multiple intracranial meningiomas
schwannomas of cranial nerves
few skin neurofibromas

Question 34

What is the definition of Menieres disease?

Answer 34

Ménière’s disease is a long-term inner ear disorder that causes recurrent attacks of vertigo, and symptoms of hearing loss, tinnitus and a feeling of fullness in the ear.

Question 35

Typical tried of symptoms in Menieres disease?

Answer 35

Hearing loss
Vertigo
Tinnitus

Question 36

Pathophysiology of Menieres disease

Answer 36

Ménière’s disease is associated with the excessive buildup of endolymph in the labyrinth of the inner ear, causing a higher pressure than normal and disrupting the sensory signals. This increased pressure of the endolymph is called endolymphatic hydrops.

Question 37

Difference between Meniere’s disease and Meniere’s syndrome?

Answer 37

Ménière’s disease is an idiopathic condition while Ménière’s syndrome results secondary to various processes interfering with normal production or resorption of endolymph e.g. - endocrine abnormalities, trauma, medications, parasitic infections and hyperlipidaemia (2).

Question 38

Epidemiology of Meniere’s disease

Answer 38

usually affects only one ear but in around 30% cases both ears may be affected (1)
The incidence is between 1:1000 and 1:2000 of the population (3).

both sexes are affected equally (3)
generally common in the fourth to sixth decades of life and consequently the incidence of new onset disease is low
a GP may expect to come across a new case only a few times in their career (1)

Question 39

Typical Presentation of Meniere’s disease

Answer 39

The typical patient is 40-50 years old, presenting with unilateral episodes of vertigo, hearing loss, and tinnitus.

Vertigo in Ménière’s disease comes in episodes. These last for 20 minutes to several hours before settling. These episodes can come in clusters over several weeks, followed by prolonged periods (often months) without vertigo symptoms. Vertigo is not triggered by movement or posture.

Hearing loss in Ménière’s disease typically fluctuates at first, associated with vertigo attacks, then gradually becomes more permanent. It is sensorineural hearing loss, generally unilateral and affects low frequencies first.

Tinnitus initially occurs with episodes of vertigo before eventually becoming more permanent. It is usually unilateral.

Other symptoms can include:

A sensation of fullness in the ear
Unexplained falls (“drop attacks”) without loss of consciousness
Imbalance, which can persist after episodes of vertigo resolve
Spontaneous nystagmus may be seen during an acute attack. This is usually in one direction (unidirectional).

Question 40

What happens in a meniere attack?

Answer 40

Attacks occur intermittently, often in clusters. Clusters may be widely separated, especially in the early stages of the disease. An attack may occur suddenly and can arise daily or as infrequently as once a year (2)

typical attack starts with cochlear symptoms which is followed by the onset of vertigo. Intensity of vertigo increases rapidly and patients may be forced to lie still. An attack may last from a minimum of 20 min to several hours (but no more than 24 hours).
prolonged attacks may be seen in some patients together with an increase in volume of tinnitus and temporary hearing loss.
patient may feel tired and nauseous after an acute attack
some patients can predict an acute attack while in others a random pattern can be observed
an attack may be triggered by diet, menstrual cycle or psychosocial stresses

Question 41

How do we make a diagnosis of Meniere’s disease?

Answer 41

Diagnosis of Ménière’s disease is clinical, based on the signs and symptoms. It will be made by an ear, nose and throat (ENT) specialist.

Patients will need an audiology assessment to evaluate hearing loss.

Question 42

Investigations of Menieres

Answer 42

To exclude systemic conditions.

renal function, glucose - metabolic disturbances
FBC, ESR, CRP - infections
TFT - hormonal imbalances (1)
For testing of hearing

pure tone audiometry:
to assess the level of hearing loss
initially, low frequencies are lost whihch resolves after an attack
later, loss of higher frequencies occurs, causing a more flattened audiogram
typically indicates a sensory type of hearing loss in the affected ear
speech discrimination is often diminished in the affected ear
For testing of balance

ENG (electronystagmograph) or video nystagmography
rotational testing (balance platform)
In addition, patients who are suspected of having Meniere’s disease, should rule out acoustic neuroma (vestibular schwannoma) by having a magnetic resonance imaging of the internal auditory meatus.

Other tests which are used in specialist clinics include:

the bithermic caloric testing an objective test of unilateral peripheral vestibular disease
ectrocochleography (ECoG) – measures the electrical activity of the inner ear
the vestibular evoked myogenic potential -
the video head-impulse test- to identify peripheral vestibular deficits

Question 43

Clinical diagnosis of Menieres disease

Answer 43

acute episodes of vertigo should be differentiated from non-rotatory dizziness
ask the question “did you just feel lightheaded or did you see the world spin around as though you just got off a playground roundabout?

no - then could be presyncope, lightheadedness, and disequilibrium in elderly people

yes - rule out “red flags” suggesting brainstem stroke or other central signs, do confirmatory test to rule out other common causes of vertigo

Hallpike manoeuvre - for benign positional vertigo, head thrust test - for acute vestibular neuritis

if both are negative consider
vestibular migraine - if vertigo plus migraine is recurrent
Meniere’s disease - transient unilateral hearing loss or tinnitus, and previous episodes of dizziness

Question 44

What is the management of Meniere’s disease?

Answer 44

Management involves:

Managing symptoms during an acute attack
Prophylactic medication to reduce the frequency of attacks

For acute attacks, short-term options for managing symptoms include:

Prochlorperazine
Antihistamines (e.g., cyclizine, cinnarizine and promethazine)

Prophylaxis is with:

Betahistine

Question 45

Prognosis of menieres disease

Answer 45

Meniere’s disease usually “burns itself out” after about 5-15 years. Although the episodes of vertigo ceases, the patient may experience a constant mild disequilibrium, tinnitus, and moderate (but not complete) unilateral hearing loss (2)