Syndromes and Lesions of Brainstem Nuclei Sudeep Bhabad, MD Vrushali Bacchav, MD Daniel L’Heureux, MD Miral Jhaveri, MD

Rule of 4 4 structures in the ‘midline’ beginning with M. 4 structures to the side beginning with S. 4 cranial nerves in the medulla, 4 in the pons and 4 above the pons (2 in the midbrain). 4 motor nuclei that are in the midline are those that divide equally into 12 except for 1 and 2, that is 3, 4, 6 and 12 (5, 7, 9 and 11 are in the lateral brainstem).

4 midline “M” nuclei 4 lateral “S” tracts Motor Pathway (Pyramidal tract) Medial Lemniscus Medial Longitudinal fasciculus Motor Nucleus of CN - XII Spinothalamic Spinocerebellar Sympathatic (rubrospinal) Spinal nucleus of CN - V ML ST SC MLF Sym Sv M 12

MIDLINE MOTOR NUCLEI CN - III Nc & N CN - IV Nc & N CN - VI Nc & N CN - XII Nc. MOTOR

BRAINSTEM NUCLEI Edinger Westphal Nc. CN - III Nc & N CN - IV Nc & N Sensory Nc. of CN – V & N. Motor Nc. Of CN - V & N Ant. & Post. Cochlear N. CN - VI & Nc CN – Vll & Nc Vestibular N & Nc. Sup. & Inf. Salivary Nc. Solitary Nc. Nucleus Ambiguus Dorsal Motor Nc. Of CN - X Hypoglossal Nc. Spinal Nc. & tract of CN - V Spinal accessory Nc. MOTOR SENSORY

Involement of Midline ‘M’otor pathways and Lateral ‘S’ tracts is “Meridian of Longitude”. The cranial nerve “the parallels of latitude” indicates whether the lesion is in the medulla (12th), pons (6th) or midbrain (3rd).

Brainstem Syndrome 1 34 yo male with diplopia, progressively worsening nausea and vomiting, headaches and ataxia with paralysis of upward gaze.

Diagnosis : Pineal Germinoma What is the Clinical Syndrome caused by Pineal Germinoma in this patient?

Parinaud syndrome Caused by direct compression of the quadrigeminal plate, which interrupts the neurons that link the cerebral cortex, the superior calculi, and the occulomotor nuclei. It is characterised by: Upward-gaze Palsy Pseudo-Argyll Robertson pupils – Paralysis of accomodation and large pupils Convergence-retraction nystagmus Eyelid retraction (Collier's sign) Conjugate down gaze in the primary position: "setting-sun sign".

Brainstem Syndrome 2 50 year old Male with diplopia and right sided ataxia and Chorea. FLAIR hyperintense peripherally enhancing lesion involving the left paramedian Midbrain.

Midbrain at Superior Colliculus RN RN 3 3 SC SC

Diagnosis: Neurocysticercosis of midbrain Location and presentation of this lesion mimics which midbrain infarction Syndrome? Answer : BENEDIKT SYNDROME Diplopia – Cochlear Nucleus right sided ataxia and Chorea – Red Nucleus

Brainstem Syndrome 3 3 3 SC SC RN RN Images used courtesy of Dr. Frank Gaillard at Radiopaedia. org (http://radiopaedia.org/images/94/).

WEBER’s SYNDROME Structure damaged Effect Substantia nigra contralateral parkinsonism because its dopaminergic projections to the basal ganglia innervate the ipsilateral hemisphere motor field, leading to a movement disorder of the contralateral body. Corticospinal fibers contralateral hemiparesis and typical upper motor neuron findings. It is contralateral because it occurs before the decussation in the medulla. Corticobulbar tract difficulty with contralateral lower facial muscles and hypoglossal nerve functions Oculomotor nerve fibers ipsilateral oculomotor nerve palsy with a drooping eyelid and fixed wide pupil pointed down and out. This leads to diplopia.

Weber’s Vs Benedict’s Syndrome Main difference between the two being involement of red nucleus in Benedikt Syndrome. Weber's is more associated with hemiplegia, and Benedikt's with hemiataxia.

Brainstem syndrome 4 39 yo male who presented with vertical diplopia, torsional nystagmus and right leg ataxia with poor gait.

Midbrain at Inferior Colliculus MLF IV IC IC

Claude Syndrome Infarct within the paramedian midbrain tegmentum, with extension from the Sylvian aqueduct. This patient presented with vertical diplopia, torsional nystagmus and right leg ataxia with poor gait. The visual disturbance is related to the involvement of the trochlear nerve nucleus and fascicles. Injury to the dentato-rubro fibers and/or red nucleus resulted in ataxia.

Hypertrophic olivary degeneration

Triangle of Guillain and Mollaret Red Nucleus dentatorubral fibres central tegmental tract Dentate nucleus olivocerebellar fibres Inferior Olivary nucleus

Hypertrophic right olivary degeneration. 57/M Post transplant lymphoproliferative disorder. A B Enhancing lesion involving the left dentate nucleus (A) with surrounding vasogenic edema. Subtle T2 signal change in the right inferior olivary nucleus due to hypertrophy olivary degeneration secondary to the left dentate nucleus lesion.

Brainstem syndrome 5 Enhancing lesion involving dorsal aspect of rostral Pons Involving the MEDIAL LONGITUDINAL FASCIUCLUS. What is the Clinical Syndrome associated with this lesion?

Rostral PONS PT PT ML ML V MCP V S MLF S M M SCP

Internuclear Ophthalmoplegia Involvement of MLF results in an ipsilateral internuclear Ophthalmoplegia (INO). INO is characterized by failure of adduction (movement towards the nose) of the ipsilateral eye and contralateral eye (leading eye) nystagmus on looking laterally to the opposite side of the lesion. e.g. If the patient had involvement of the left MLF then, on being asked to look to the left, the eye movements would be normal, but on looking to the right the left eye would not go past the midline, while there would be nystagmus in the right eye as it looked to the right. P. GATES, Internal Medicine Journal 2005; 35: 263–266

Medial longitudinal fasciculus (MLF) MLF is heavily myelinated tract in the brain stem that connects the nuclei of the 3rd, 4th, 6th and 8th cranial nerves. This pathway provides a neural mechanism for simultaneous contraction of the lateral rectus muscle on the one side and the medial rectus muscle on the opposite side, required for conjugate lateral gaze. The vertical gaze center is at the rostral interstitial nucleus (riMLF). The MLF ascends to the interstitial nucleus of Cajal, which lies in the lateral wall of the third ventricle, just above the cerebral aqueduct. MLF is the main central connection for the oculomotor nerve,trochlear nerve, and abducens nerve.

MLF Pathway Axons from the canal project to the ipsilateral vestibular nuclei and then decussate to innervate the contralateral inferior rectus subnucleus of the oculomotor complex of cranial nerve III and the trochlear nucleus. The trochlear neurons then exit the brainstem posteriorly and decussate back to the left side innervating the superior oblique muscle. Activation of both canals (as with pitching the head upward and attempting straight ahead fixation) will result in cancellation of the torsional vector components, but addition of the vertical vector components resulting in downward movement of the eyes. http://www.neurology.org/content/70/17/e57.full.pdf+html Vestibular Nystagnus COWS: Cold Opposite, Warm Same Cold water = FAST phase of nystagmus to the side Opposite from the cold water filled ear Warm water = FAST phase of nystagmus to the Same side as the warm water filled ear In other words: Contralateral when cold is applied and ipsilateral when warm is applied

Trigeminal nucleus lesions 32/F with left tongue and peri -oral numbness. PT PT ML ML V V S MLF S M M Subtle enhancing FLAIR hyperintense demyelinating lesions in the region of the right facial colliculus and left trigeminal nucleus.

Facial colliculus Syndrome Brainstem syndrome 6 Facial colliculus Syndrome Same 32 yo Female patient with MS also had diplopia. Subtle enhancing FLAIR hyperintense demyelinating lesions in the region of the right facial colliculus and left trigeminal nucleus.

Facial Colliculus – Caudal Pons PT PT 5 8V 8C

Facial Colliculus lesion 61/M Multiple sclerosis with diplopia and paralytic strabismus, left sixth nerve palsy. C A B Enhancing lesion in the left lateral aspect of the pons near the facial colliculus in the region of the left sixth nerve nucleus.

62 yo male with dizziness with slight anisocoria (L>R) restricted lateral gaze bilaterally, left lower>upper facial weakness, dysarthric speech. Focal area of restricted diffusion in the dorsal aspect of pons in the region of the facial colliculus.

One-and-a-half syndrome Brainstem syndrome 7 One-and-a-half syndrome ipsilateral conjugate horizontal gaze palsy (the "one") and an ipsilateral internuclear ophthalmoplegia (INO) (the "half"). This is caused by a lesion that affects the ipisilateral paramedian pontine reticular formation (PPRF) or the abducens (CN IV) nucleus (responsible for the horizontal gaze palsy) and the ipsilateral medial longitudinal fasciculus (MLF) (responsible for the INO - failed adduction of the ipsilateral eye). The only remaining horizontal movement is contralateral abduction. The apparent adduction deficits can be overcome with convergence. This patient showed signs of right facial weakness (forehead weakness, orbicularis weakness, ectropion, mouth droop). Along with a right horizontal gaze palsy that was not overcome with vestibulo-ocular reflex and an adduction deficit in the left eye. Adduction was preserved in both eyes with convergence. http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/eight-and-a-half%20syndrome/index.htm

Eight-and-a-half syndrome Brainstem syndrome 8 Eight-and-a-half syndrome One-and-a-half syndrome + 7th nerve palsy = eight-and-a-half syndrome. When this lesion also affects the fascicle of the the ipsilateral facial nerve (CN VII) in the region of the facial colliculus as it wraps around the CN VI nucleus, it produces a lower motor neuron pattern of ipsilateral facial weakness. When this occurs, a one-and-a-half syndrome plus a 7th nerve palsy, it is termed an eight-and-a-half syndrome.

Brainstem Syndrome 9 3 year old male with acute onset ataxia, leading to his left while walking, repeated emesis, Horner’s syndrome. H/o fall on head an hour before the symptoms started. H/o recent travel to Puerto Rico Mother had 2 miscarriages.

Lateral Medullary Syndrome (Wallenberg Syndrome) What is this stroke Syndrome?

Rostral MEDULLA Vs Vs PT ION ML ST SC A S X ST ICP VIII XII XII MLF Rub Vs ICP Vs XII XII S X VIII

Lateral medullary syndrome (Wallenberg syndrome) ipsilateral deficits in pain and temperature over face (spinal trigeminal nucleus involvement) ataxia and in-coordination (inferior cerebellar peduncle) dysarthria/dysphagia/decreased gag (nucleus ambiguus) contralateral deficits in pain and temperature over trunks and limbs vertigo (vestibular nucleus)

59 / M left sided numbness, fall with right sided weakness. Brainstem syndrome 10 59 / M left sided numbness, fall with right sided weakness. A B C Punctate acute infarct in the medial aspect of medulla on the left.

Medial medullary syndrome (Dejerine syndrome) Hypoglossal nerve fibers – Deviation of the tongue to the side of the infarct on attempted protrusion, caused by ipsilateral muscle weakness. Medullary pyramid (corticospinal tract)- Contralateral hemiplegia Medial leminiscus – loss of discriminative touch,  proprioception, and vibration sense on the contralateral side of the infarct

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