Session 7:Neoplastic & Autoimmune CNS Disorders

Vignette

A 23 yo med student with a 2 day history of headache, blurred/darker vision/loss of vivid color. There is accompanying left retro-orbital pain which worsens with eyemovement. She has never had anything like this before, and past medical history is negative. • Anatomical localization?

Questions

• Exam: L eye 20/100; R 20/20; L disc is edematous; pupils are equal but when light is shined into L eye pupils are 4mm; and 2 mm when shined into R eye. R gaze: L eye adducts more slowly than the R eye. L gaze eyes are conjugate. Enlarged blind spot noted on the L.

• Does the examination refute or support localization?

• Cause for visual impairment

Questions

• Visual acuity

• Light reaction

• Eye movements

• Visual fields

• Cause of visual impairment

• Cause of eye movement difficulties

Questions

• ROS

• PMHx

• Tests

• Diagnosis

• Certainty and how is diagnosis is made

• What is the outlook?

• What do you disclose?

MRI Scans of the Brain of a 25-Year-Old Woman with Relapsing–Remitting Multiple Sclerosis.

An axial FLAIR (fluid-attenuated inversion recovery) image shows multiple ovoid and confluent hyperintense lesions in the periventricular white matter (Panel A). Nine months later, the number and size of the lesions have substantially increased (Panel B). After the administration of gadolinium, many of the lesions demonstrate ring or peripheral enhancement, indicating the breakdown of the blood–brain barrier (Panel C). In Panel D, a parasagittal T1-weighted MRI scan shows multiple regions in which the signal is diminished (referred to as "black holes") in the periventricular white matter and corpus callosum. These regions correspond to the chronic lesions of multiple sclerosis.

Multiple sclerosis: This 35-year-old woman with a history of migraine headaches presented with a two-week history of slurred speech and trouble walking. Her examination was significant for slight left hemiparesis, brisk jaw jerk and bilateral hyperreflexia. Laboratory data demonstrated oligoclonal banding in the cerebrospinal fluid. These FLAIR-weighted axial MR images show multiple high signal lesions within the periventricular white matter. On the sagittal image on the right the signals emanate radially from the corpus callosum.

Optic Neuritis with a swollen optic nerve

The optic disc is pale. Note: if the patient is pseudophakic in one eye and has cataract in the other, the disc in the pseudophakic eye may appear paler in the absence of optic atrophy. The following features may help in the diagnosis.  •Excavated appearance with the blood vessels dipping the edge (glaucoma) •Indistinct edge with glial tissue (chronic papilloedema) •Well-defined edge without excavation (optic nerve disease)

Look for: in young patient: internuclear ophthalmoplegia and cerebellar sign for multiple sclerosis; in old patient, look for vascular diseases such as prominent temporal artery (or old scar indicating temporal artery biopsy) and carotid bruit  (or endarterectomy scar)

Optic atrophy

The arrows represent the light.

This is a common case in pupillary examination. Always suspect this if there is no anisocoria. The direct and consensual pupillary responses to light are normal. The swinging light test shows abnormal light response of the affected eye (initial dilatation followed by constriction). For example, if the left eye were abnormal, both pupils constrict when the light is shown into the right eye. When the light is swung to the left eye, both pupils dilate. When the light is swung back to the right eye both pupils again constrict. This reaction indicates a defect in the afferent pupillary fibres from the left eye. The near reflex is normal.

Further examination: tell the examiner that you would like to examine the fundus of the affected eye. The most common physical signs would be optic atrophy. Other possibilities include advanced glaucoma, retinitis pigmentosa, old central retinal artery or vein occlusion.

A patient with a left relative afferent pupillary defect.

Relative afferent pupillary defect

Fig.1 A patient with a right dilated and unreactive pupil. The swinging flash test shows abnormality of the left eye. (Note the dilatation of the left eye when the light is swung to the left.)

Fig. 2 A patient with a right dilated and unreactive pupil. The swinging flash test shows abnormality of the right eye  (Note dilatation of the left eye when the light is swung to the right).

The most common scenario in the examination is young female with history of multiple sclerosis. However, it can also be seen in older patients with cerebrovascular accident. The main feature of this condition is impaired adduction. A favourite question is the site and side of the lesion (see question below).

In unilateral case, the affected eye shows failure (or impaired) adduction (failure of conjugate eye movement). The abducting eye shows jerk nystagmus with the quick phase towards the opposite side (this is called ataxic nystagmus but may not be obvious and  can be absent). The horizontal saccade is abnormal with the affected eye lagging behind the normal eye. The vertical saccade and convergence are normal.

Left internuclear ophthalmoplegia

R L

a. Normal primary position b. Left impaired adductionn on right gaze

c. Normal left abduction on left gaze d. Normal convergence

Internuclear ophthalmoplegia (INO)

Impact on Visual Fields

• Left optic nerve lesion

• Optic chiasmal lesion

• Left temporal lobe lesion

• Left occipital lobe lesion

Visual Pathways

1. Central scotoma resulting from inflammation of the optic disc

2. Junctional scotoma

3. Bitemporal hemianopia resulting from a lesion around the optic chiasm

4. Incongruous homonymous hemianopia resulting from a lesion in the optic tract

5. Homonymous quadrinopia resulting from a lesion in the temporal lobe

6. Homonymous hemianopia resulting from a lesion in the occipital lobe.

The peripheral visual fields are normal in both eyes. There is a right central scotoma (revealed by testing the central field with a red pin). Note: the most likely diagnosis is optic neuritis.

Further examination:  •Examine the patient's fundus for any evidence of papillitis or optic atrophy. Also check for relative afferent pupillary defect. •Look for cerebellar signs or spastic paresis which are common in patients with multiple sclerosis.

1. Central scotoma resulting from inflammation of the optic disc

The patient has a right central scotoma and left superior temporal field defect. This suggests a lesion between the optic nerve and the chiasm on the side with the central scotoma. There is compression of the knee of Wilbrand (loop of inferior nasal fibers) that enter the contralateral optic n for a short distance before travelling in the optic tract. Examine for optic atrophy on the side with central scotoma and possible papilloedema on the other side. The most common causes are meningioma and a prefixed pituitary tumour. In the former, the patient may have proptosis and in the later signs of hypopituitarism or acromegaly.

2. Junctional scotoma

There is bitemporal hemianopia which obeys the midline.and suggests a lesion in the optic chiasm. The hemianopia may be subtle and revealed only by comparing two red objects in each hemifield. The red color in the temporal field appears washed out. If the hemianopia does not obey midline consider pseudo-bitemporal hemianopia such as bilateral sectorial retinitis pigmentosa, tilted discs or bilateral inferotemopral retinoschisis. Examine the fundi for any such changes.Features of pituitary abnormalities such as acromegaly, pan-hypopituitarism (smooth skin and absence body hair in male) Look for any scar suggestive of pituitary operation.

3. Bitemporal hemianopia resulting from lesion around the optic chiasm

The patient has a left incongrous homonymous hemianopia suggesting lesion in the right optic tract. Optic tract lesion causes homonymous hemianopia which is incongrous (meaning that the shape of the defect is different in the two half fields). This can be established on confrontation if significant. If subtle it is best documented with formal field test. In the examination, optic tract lesions are often associated with contralateral pyramidal signs (due to damage to the cerebral peduncle).

4. Incongruous homonymous hemianopia resulting from lesion in the optic tract

The optic radiations are in the temporal and parietal lobes. A left superior homonymous quadrinopia is associated with a temporal lobe lesion whereas a left inferior homonymous quadrinopia is seen with a parietal lobe lesion.  During examination describe the visual field as the patient sees it. Mention if the field defect is congruous (behind the lateral geniculate body) or incongruous (in the optic tract). Look for other neurological signs such as hemiplegia.

5. Homonymous quadrinopia from lesion in the temporal lobe

Left inferior homonymous quadrinopia

Left superior homonymous quadrinopia

If the patient has a right inferior quadrinopia, you should consider Gertmann's syndrome if the lesion is in their dominant parietal lobe. What is Gertmann's syndrome?

Failure of the person to calculate (acalculia), name fingers (finger agnosia), and to tell right from left

In patients with hemianopia or inferior quadrinopia, mention you like to perform the optico-kinetic drum test for evidence of parietal lobe lesion. What abnormality may you see? Impaired pursuit to the side of the parietal lobe lesion.

Normal opticokinetic nystagmus with  smooth pursuit movement.

Abnormal opticokinetic nystagmus with  small saccadic movement replacement the  smooth pursuit movement.

Which other higher sensory perceptions are impairedAstereoagnosia (failure to tell an object through touch)Joint position sense loss and loss of two point discrimination

How do you test for sensory inattention?With the patient’s eyes closed alternatively touch the patient’s right then left hand (to ascertain that primary sensory function is intact) and then touch both hands simultaneously. If there is sensory inattention (neglect) the individual will only notice the touch on one side when touched simultaneously.

Demonstrate a central scotoma

Impact on a Rightward Saccade

• Left middle cerebral artery infarct

• Left frontal lobe seizure

• Right pontine infarct

• Left medial longitudinal fasisculus lacune

• Left diabetic third nerve palsy

Movement Definition Associated structure

Saccade

Pursuit

Oculovestibular

Convergence

1) Saccade

2) Pursuit Function: to keep the fovea on a small moving target, e.g. tracking a tennis ball.As in saccades, pointing the fovea at this moving ball is a 2D problem.

3) Vestibular ocular reflex/ Oculovestibular reflex Function: to keep the image of the world stationary on the retina when the head rotates. Try shaking your head while reading this sentence. The fact that you can do this means that your VOR is working, it is keeping your eye still in space.It does this by rotating the eyes in the opposite direction of the head.

4) Vergence/convergence Function: to align a near target on the fovea of each eye.

Vertical Saccade

• Vertical saccades originate from burst neurons in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF).

• The riMLF, like PPRF, produces the phasic command.

• Neurons in the interstitial nucleus (INC) convert this to a tonic command (like the pph for horizontal saccades).

• The phasic and tonic commands combine in the MN's in III & IV n.

• Both sides of the brainstem have neurons that generate upward saccades and others that generate downward saccades.

• Do neurons on each side do the same thing; i.e. is this a redundant representation?

Horizontal saccades

• Saccades are one of 5 types of eye movements. They are used to point your fovea quickly from one object of interest to another, such as the words of this sentence.

• The command for a saccade begins in a structure called the Paramadian Pontine Reticular Formation; the PPRF

• Burst neurons in the PPRF generate phasic movement command which is proportional to velocity

• Tonic neurons in prepositus hypoglossi (PPH)

– converts the phasic command to a tonic command

– this is like an integrator which converts velocity to position

• Motorneurons (MN's) combine phasic and tonic commands

– this contracts muscles – quickly rotates the eyes (phasic

component) – & then holds (tonic component) them there

against the elastic restoring forces.

Vestibular Control of Eye Movements

Questions

A. Carotid ArteryB. Trochlear Nerve IVC. Maxillary Nerve V2D. Abducens Nerve VIE. Sphenoid SinusF. Pituitary GlandG. Cavernous SinusH. Ophthalmic Nerve V1I. Oculomotor Nerve III

IIIIV

V1

V2

VI

Contents of the cavernous sinus (red)

Carotid-Cavernous sinus fistula

- Horner's syndrome + cranial nerve 3 and/or 4 and/or 6 and/or V1/V2 dysfunction (and not affecting V3) => suspect cavernous sinus pathology - Horner's syndrome + cranial nerves 3 and/or 4 and/or 6 and/or V1 (and not affecting V2 and V3) dysfunction => suspect superior orbital fissure pathology - Horner's syndrome + cranial nerves 2 (optic nerve), 3, and/or 4 and/or 6 and V1 (and not affecting V2 and V3) dysfunction => suspect orbital apex pathology - Horner's syndrome + optic nerve II dysfunction +/- incomplete cranial nerve 3 dysfunction (and not affecting cranial nerves 3, 4 and 6 and V2 and V3) => suspect posterior orbit pathology

- all patients with an asymptomatic, unexplained Horner's syndrome (especially if they have ipsilateral anhidrosis of the face and neck, which implies a preganglionic Horner's syndrome), who are going to be discharged from the ED for pre-arranged follow-up as an outpatient, should have a chest X-ray performed prior to ED discharge - to exclude a mediastinal or apical lung tumor (Pancoast's tumor) or thoracic aneurysm affecting the second neuron

Structural Abnormality

Orbit

Superior orbital fissure

Cavernous sinus

Upper brainstem

Autonomic Pupillary Innervation

• Sympathetic (Horner syndrome)

• Parasympathetic (IIIrd nerve)

For patients with a normal light reaction and whose anisocoria is greatest in the dark => the smaller pupil in the dark is the abnormal pupil (dilation problem with the smaller pupil)

Differentiation between physiological anisocoria and Horner's syndrome

Right Horner’s syndrome:PtosisMiosisAnhydrosisVasodilatation

Unexplained unilateral Horner's syndrome + face/head pain is a carotid artery dissection until proved otherwise

Causes of Horner's syndrome

Central Preganglionic Postganglionic

 Hypothalamus  - infarct  - tumor  Brainstem  - ischemia  - hemorrhage  - tumor  - demyelination (MS)  Cervical cord  - trauma  - tumor  - syrinx  - AVM

 Cervico-thoracic spinal roots  - trauma  - intramedullary or paravertebral tumor  - syrinx  - AVM  - spondylosis  - epidural anesthesia  Lower brachial plexus  - birth trauma  - acquired trauma  Pulmonary apex (under subclavian artery)  - vascular anomalies  - Pancoast's apical lung tumor  - cervical rib  - iatrogenic (chest tube, central catheter)  - infection (eg. apical TB)  Anterior neck  - iatrogenic (thyroid or neck surgery)  - trauma  - tumor   

 Superior cervical ganglion  - iatrogenic (tonsillectomy)  - trauma  Internal carotid artery  - dissection  - trauma  - thrombosis  - tumor  - cluster headache  Base of skull/carotid canal  - tumor (nasopharyngeal CA)  - trauma  Middle ear  - tumor (cholesteatoma)  - infection  Cavernous sinus  - tumor (pitutary adenoma)  - inflammation (Tolosa Hunt)  - cavernous carotid aneurysm  - thrombosis  - fistula

Clinical Pearls - if there is a ptosis of the eyelid on the side of the small pupil => the patient has a Horner's syndrome on that side - if there is a ptosis of the eyelid on the side of the large pupil => the patient has a partial third nerve lesion on that side - with a lesion in the region of the cavernous sinus, there may actually be a reversal of the anisocoria in going from dark to light as a result of unilateral involvement of both parasympathetic and sympathetic axons - a patient with a very small unilateral miotic pupil, that does not decrease in size in response to direct bright light, or dilate in response to dim light => probably has unilateral pharmacolgical miosis secondary to a cholinergic glaucoma drug (eg. pilocarpine) or an anti-cholinesterase agent ("flea collar" anisocoria) - a mydriatic pupil that does not respond to light may appear to be due to 3rd cranial nerve pathology, but it could just be a tonic pupil - the only difference between the two may be that the tonic pupil does eventually constrict slowly on prolonged near fixation - a patient with uncal herniation causing a compressive 3rd cranial nerve palsy, always has some degree of impairment of LOC and is never fully alert - a patient with "apparent" physiological anisocoria may have simple anisocoria secondary to the effect of certain drugs eg. pseudo-ephedrine or serotonin reuptake inhibitors, and the anisocoria (like physiological anisocoria) is also eliminated by the instillation of cocaine eyedrops - blindness in one eye (even if total) never causes anisocoria - retinal pathology (even if very severe) never causes anisocoria

Pupil sparing CN III palsy suggests diabetes.

For patients with an abnormal light reaction and whose anisocoria is greatest in bright light conditions => the larger pupil is the abnormal pupil (constriction problem with the larger pupil)

Left IIIrd nerve palsy

Left IIIrd nerve palsy

An 86 year old man has come to your clinic for an evaluation of back pain. He has had prostate cancer for two years. His back pain has been present for weeks "off and on", but has started to shoot across the right side of his back, below the rib cage. In the last few days, he has noticed some numbness of the left leg. He does very little walking, but can walk between rooms in his apartment with help. Some urinary symptoms date back years; he is continent. He says he has already told his primary care physician that he does not want aggressive treatment when "the inevitable" happens.

Vignette

• The physical examination reveals a lucid but very frail man, who can rise from a chair and take several steps only with considerable help. His gait is not noticeably asymmetric. There is tenderness over the T10 vertebra. Although he is frail, strength is full except for mild right lower extremity weakness. The DTRs in the arms are symmetric, the right knee reflex is greater than the left and ankle reflexes are absent bilaterally. There is a positive Babinski sign on the right, not on the left. Sensation to pin is diminished in the left leg, up to about mid-thigh in front and through the perineal area in back.

• What is the anatomic diagnosis? •  How do you account for the differing laterality of motor

(reflex) and sensory signs, and what is this called?•  What process is involved? What would be your differential

diagnosis for this kind of deficit if the patient had not had a history of cancer?

•  What imaging tests are available for the area you wish to investigate, and what are their uses? Which would you pick for this patient?

•  What treatments are available? • How urgent is evaluation and treatment?  Would your

approach be different if there were back pain without neurological signs?

Vignette

• A 34 year old man develops gait difficulty and numbness below the mid-chest 2 weeks after an upper respiratory illness. Examination demonstrates diminished pin sensitivity below the mid-chest, absent abdominal reflexes, sustained ankle clonus and bilateral Babinski signs. He has a spastic gait.

Brown SequardMuscles: -no muscle control on the same side of the body that the lesion occurredSensation: -no sensation of  “touch” on the same side of the body that the lesion occurred -no pain and temperature sensation on the opposite side of the body that the lesion occurredOther:  -fairly often have normal bowel and bladder functioning

Anterior CordMuscles: -variable muscle control throughout body Sensation: -variable sensation of touch, temperature and pain throughout body, however can sense where limbs are in space

Central CordMuscles: -upper limbs are weaker than lower limbs Sensation: -maintain most sensations Other: -this injury usually occurs in the cervical region

Posterior CordMuscles: -can control most muscles throughout bodySensation: - no sensation of touch, temperature and pain

Cauda EquinaMuscles: -no muscle movement in certain muscles in the lower limb Other:  -may cause incontinence-this part of the spinal cord is actually made of nerves, nerves (unlike the spinal cord) have the ability to heal and therefore there is a chance that some muscle control will return after a cauda equina injury (This is an injury to the nerves that exit at the base of the spinal cord)

High signal change in spinal cord on T2 weighted MRI

Vignette

• A 57 year old man develops gradually progressive left-sided headaches clumsiness in the right hand over 6 months’ time. Examination demonstrates moderate slowing of rapid repetitive movements in the right hand and foot, 3+ reflexes throughout the right and 2+ reflexes throughout the left.

Vignette

• A 67 year old woman with a history of breast cancer develops progressive left-sided headaches and clumsiness in the right hand over 6 weeks’ time and loss of appetite. Examination demonstrates mild attentional difficulty, a left homonymous hemianopsia, moderate slowing of rapid repetitive movements in the right hand and foot, and bilateral Babinski signs.

Enhanced CT shows 3 cm mass right frontal region with extensive vasogenic white matter edema with mass effect, midline shift.

Brain Metastasis - Lung Carcinoma Right Frontal Lobe

Vignette

• A 31 year old woman with fever, anemia, and a facial rash is admitted to the hospital with an acute confusional state.

Vignette

• A 36 year old woman develops a Bell’s palsy for the second time in 9 months with headache and unilateral hearing loss. Examination demonstrates a right facial palsy, left sided hearing loss, and patchy hyporeflexia; chest x-ray demonstrates hilar adenopathy.

Vignettes

• Idiopathic intracranial hypertension

• Cerebral venous thrombosis

77 year old male with decreased libido

Findings T1 sagittal image shows aheterogenous mass centeredprimarily in the sella with largesuprasellar extension. T2 coronalimage shows predominantlyhypointense signal in this mass.Post contrast coronal imageshows heterogenousenhancement and extension ofthis mass into right cavernoussinus.

Diagnosis: Pituitary Prolactinoma

• Reference: Diagnostic Neuroradiology, Anne G. Osborn

• Contributor: Harish Patel , M.D

• Discussion Common intrasellar masses include physiologic hyperplasia, microadenoma and nonneoplastic cyst { Rahtke's cleft cyst }. Of these, none fit the description of this extensive mass. The list can be long to include suprasellar lesions like meningioma, craniopharyngioma, pituitary macroadenoma, hypothalamic/chiasmatic glioma and aneurysm

• Prolactinomas are the most common pituitary adenomas, accounting for about 30%. They occur in young women causing amenorrhea and galactorrhea, and in elderly male causing decreased libido. Patients have elevated serum prolactin levels as in this case. This study was performed for a follow up evaluation after Bromocriptine therapy . Bromocriptine is the medical treatment and often shows size reduction within a week of therapy.