ADD-ONS / GENERAL NEUROLOGY

Brainstem syndromes

David Goldemund M.D.
Updated on 03/06/2024, published on 27/05/2024

Notes on topical diagnosis of brainstem lesions

  • the brainstem is composed of three main parts: the medulla oblongata, pons, and midbrain (mesencephalon)  Brainstem anatomy on MRI
  • each part of the brainstem consists of
    • gray matter – cranial nerve nuclei, nuclei of the reticular formation (RF), etc.
    • white matter (compact or dispersed bundles)
      • afferent sensory pathways
        • the pathway for proprioception, vibration, and fine touch (medial lemniscus) is located more medially
        • crude touch and pressure sensations are transmitted via the anterior spinothalamic tract
        • the pathway for pain and thermal sensation (lateral spinothalamic tract) is located more laterally
      • efferent motor pathways
      • other pathways (FLM, sympathetic pathways, etc.)
  • even small lesions can lead to significant clinical symptoms due to the high density of critical structures; symptoms depend on the extent and the location of the lesion in the brainstem (both at the vertical and the horizontal level)
  • lesions of the long tracts passing through the brainstem allow for transversal localization of the lesion (lateral x medial or tegmentum x base)
  • assessment of cranial nerves function:
    • allows precise (motor nuclei) or less precise (some columnar nuclei such as ncl. ambiguus) vertical localization of the lesion
      • medulla oblongata = CN VIII-XII, pons = CN V-VII,  midbrain = CN III-IV
    • refines transverse topography as the nuclei are arranged in a mediolateral order: motor efferent – autonomic efferent – sensorimotor afferent – sensory afferent nuclei
      • lateral lesions cause Horner’s syndrome, lesions of CN V, VII, or VIII, and involvement of the lateral spinothalamic tract, cerebellar peduncles, or vestibular pathways
      • medial lesions affect CN III, IV, VI, XII, pyramidal tract, medial lemniscus, longitudinal medial fascicle (LMF)
  • localized brainstem lesions (most commonly vascular) present with typical alternating syndromes (Weber, Millard-Gubler, Dejerine, etc.)
    • on the side of the lesion (ipsilaterally), there is a specific cranial nerve lesion (nuclear/fascicular), Horner syndrome, gaze palsy, cerebellar syndrome, etc.
    • contralaterally, funicular lesions typically occur (hemiparesis, hemihypesthesia, hemichorea/hemitremor, hemiataxia)

Topography of localized brainstem lesions

Numerous brainstem syndromes named after their discoverers have been described. Knowledge of eponyms of brainstem syndromes has questionable clinical relevance, as their clinical presentation is often modified or they are very rarely encountered. A morpho-functional classification is preferred over the use of eponyms. According to anatomical localization, the following syndromes are listed, including their vascular territories and clinical manifestations.

medulla oblongata pons mesencephalon
medial medial inferior
mid-pons
superior		 medial inferior
mid-mesencephalon
lateral
 lateral 
 inferior
mid-pons
superior 
 lateral inferior
mid-mesencephalon
dorsal

Vascular supply of the brainstem

Medulla oblongata

The medulla oblongata, located in the foramen magnum, continues from the spinal cord and connects cranially to the pons Varolii. It contains the nuclei of the distal cranial nerves IX-XII (as well as parts of the nuclei of the trigeminal nerve), all ascending spinal tracts, and the tracts descending to the spinal cord from higher levels of the CNS. The ventral part features the decussation of the pyramids. Dorsally, between the inferior cerebellar peduncles, lies the caudal part of the fourth ventricle, beneath whose floor are the vestibular nuclei and a dispersed array of nuclei of the reticular formation. These nuclei are crucial in regulating respiration, cardiac activity, blood pressure, and circulation.

Medullary syndrome (medial=green, lateral=blue)

Medial medullary syndrome (Dejerine)

  • occlusion of the anteromedial branches of the anterior spinal artery (ASA) and vertebral artery (VA)
  • damage to the motor nucleus of the hypoglossal nerve (CN XII), corticospinal tract, medial lemniscus, and possibly the medial longitudinal fasciculus (MLF)
  • clinically:
    • ipsilaterally:  flaccid paralysis and atrophy of one half of the tongue (lesion of the nucleus and/or fascicles of the hypoglossal nerve)
    • contralaterally:
      • spastic hemiparesis (corticospinal tract)
      • impaired tactile, proprioceptive, and vibration sense of trunk and limbs (medial lemniscus)
    • bilateral Dejerine’s syndrome presents with quadriparesis and glossoplegia Bilateral Djerine syndrome [Tsetsou, 2016]

Lateral medullary syndrome (Wallenberg syndrome)

  • one of the most common vascular brainstem syndromes
  • caused by the occlusion of PICA or perforators from the vertebral artery
  • clinical presentation:
    • vertigo, nystagmus, nausea (vestibular nuclei and their connections)
    • sometimes hiccups
    • dysphagia, dysarthria, dysphonia, ↓ gag reflex (nucleus ambiguus, nucleus tractus solitarius/solitary nucleus)
    • ipsilateral
      • ipsilateral loss of thermoalgesic and tactile sense over the face; absent corneal reflex (trigeminal nerve)
      • Horner’s syndrome (sympathetic pathway)
      • limb hemiataxia (inferior cerebellar peduncle)
    • contralateral
      • loss of pain and temperature sense over the contralateral side of the body (spinothalamic tract)
Wallenberg syndrome
Wallenberg syndrome
Dejerine syndrome

Babinski-Nageotte syndrome

  • caused by hemimedullary infarction and combines the medial and the lateral medullary syndromes

Avellis syndrome

  • caused by a small lesion (most commonly lacunar infarct) in the lateral medulla oblongata
  • it presents with alternating hemiplegia with ipsilateral palatopharyngeal paresis due to a lesion of the upper part of the nucleus ambiguus and contralateral loss of pain/temperature sense
Palatal paresis
Avellis syndrome on MRI

Hemiplegia cruciata

  • partial lesion of the pyramidal decussation
  • clinical presentation:
    • ipsilateral: lesion of the already crossed tract for the lower limb
    • contralateral: paralysis of the upper limb
Hemiplegia cruciata

Pons Varoli

The pons Varoli got its name because, when viewed from the ventral side of the brain, it appears to connect both cerebellar hemispheres with its arms. In the caudocranial direction, it connects the medulla oblongata and the midbrain.

Inferior pontine syndrome (medial=green, lateral=blue)

Medial inferior pontine syndrome (Millard-Gubler)

  • lesion of the caudal paramedian (anteromedial) perforators of the basilar artery
  • lesion is localized in the ventromedial caudal pons
  • clinical presentation:
    • ipsilateral
      • diplopia on lateral gaze (lesion of CN VI)
      • ataxia (middle cerebellar peduncle)
    • contralateral
      • hemiparesis (corticonuclear and corticospinal tract)
      • disturbance of tactile, proprioception, and vibration senses (medial lemniscus)

Foville syndrome

  • ipsilateral:
    • facial weakness (lesion of CN VII)
    • conjugate gaze palsy of horizontal eye movement towards the side of the lesion (paramedian pontine reticular formation -PPRF)
  • contralateral:
    • hemiparesis (corticospinal tract)

Lateral inferior pontine syndrome

  • lesions of the laterocaudal perforators originating from AICA
  • affected structures include the nuclei of cranial nerves V, VI, and VII, vestibular and cochlear nuclei, the center for conjugate horizontal gaze (PPRF), the middle cerebellar peduncle, and the spinothalamic tract
  • clinical presentation:
    • gaze paresis towards the side of the lesion
      • deviation of the eyes to the opposite side (away from ischemia), which is the opposite to deviation caused by MCA infarcts
    • ipsilateral:
      • facial paresis (CN VII) and paresis of CN VI
      • lesion of CN V
        • impaired tactile sensation in the face with an absent blink reflex
        • impaired thermal and pain sensation in the face (spinal nucleus of cranial nerve V)
        • impaired mastication
      • hemiataxia and intention tremor (superior cerebellar peduncle)
      • +/- Horner’s syndrome
    • contralateral:
      • loss of temperature and pain sensation (lateral spinothalamic tract)
      • hypesthesia and impairment of deep sensation (medial lemniscus)
    • additionally, vertigo, nausea, nystagmus, tinnitus, and deafness (lateral lemniscus) may occur
Superior pontine syndrome (medial=green, lateral=blue)

Medial superior pontine syndrome

  • occlusion of paramedian and short circumferential branches of the basilar artery
  • clinical presentation:
    • ipsilateral
      • paresis of masticatory muscles (CN V)
      • sensory disturbance over the face for all modalities
      • hemiataxia (middle cerebellar peduncle)
    • contralateral
      • hemiparesis (corticospinal tract)

Lateral superior pontine syndrome

  • occlusion of circumferential branches of the basilar artery (BA) and branches of the superior cerebellar artery (SCA)
  • clinical presentation:
    • ipsilateral
      • hemiataxia, intention tremor (superior cerebellar peduncle)
      • hypesthesia in the face and difficulty chewing (lesion of the CN V)
    • contralateral
      • hemiparesis
      • hemianesthesia

One and half syndrome

  • combination of nuclear and internuclear ophthalmoplegia
  • lesion of the caudal dorsal pontine tegmentum affecting the ipsilateral paramedian pontine reticular formation (PPRF) or the abducens nucleus and the ipsilateral medial longitudinal fasciculus (MLF)
  • the result is ipsilateral horizontal gaze palsy + internuclear ophthalmoplegia (evident when looking in the opposite direction!)
    • on the side of the lesion, no horizontal eye movement is possible; contralaterally, only abduction is possible
One and half syndrome - lesion is on the left side

Mesencephalon

Inferior mesencephalic syndrome (medial=green, lateral=blue)

Medial inferior mesencephalic syndrome

  • paramedian branches of the basilar artery
  • clinical presentation:
    • ipsilateral
    • contralateral
      • lesion of the CN IV
      • ataxia (superior cerebellar peduncle)
      • impaired proprioception and discriminatory sensation (medial lemniscus)
      • hemiparesis (corticospinal tract)

Lateral inferior mesencephalic syndrome

  • territory of the SCA and PCA
  • clinical presentation
    • ipsilateral
      • Horner syndrome (damage to central sympathetic pathways)
      • facial sensory disturbance (nucleus of the CN V)
    • contralateral
      • thermoalgesic hemianesthesia (lateral spinothalamic tract)
Mid-mesencephalic syndrome (medial=green, lateral=blue)

Medial mid-mesencephalic syndrome

Weber syndrome (superior alternating hemiplegia)

  • lesion of interpeduncular perforating branches of the BA and branches of the PCA (posterior choroidal artery)
  • clinical presentation
    • ipsilateral
      • oculomotor nerve palsy (CN III fascicles)
        • ptosis, dilated pupil, the eye is shifted downwards and outwards
    • contralateral
      • spastic hemiparesis (corticospinal tract)
    • Weber syndrome may be associated with Parkinsonian rigidity (if the lesion reaches substantia nigra)
Medial mid-mesencephalic syndrome on MRI

Lateral mid-mesencephalic syndrome

Claude syndrome

  • lesion of interpeduncular perforating branches of the BA and branches of the PCA
  • clinical presentation:
    • ipsilateral
      • oculomotor nerve paresis (CN III fascicle)
    • contralateral
      • impaired tactile and deep sensation (medial lemniscus)
      • hemitremor (red nucleus)
      • cerebellar ataxia (superior cerebellar peduncle) 

Benedikt syndrome

  • clinical presentation: a combination of Weber and Claude syndromes

Dorsal mesencephalic syndrome (Parinaud syndrome)

→ see the separate chapter about Parinaud syndrome

Other brainstem syndromes

Locked-in syndrome

Pathophysiology

Synonyms: De-efferentation state, pseudocoma, Sy Monte Cristo, Filimon’s syndrome, ventral pontine syndrome, ventral brainstem syndrome, cerebromedullary disconnection syndrome

  • the only sign of a wakeful state is the preservation of voluntary vertical eye movements
  • syndrome is typically caused by lesions at the base of the brainstem (usually in the pons or midbrain), which damage efferent motor pathways (de-efferentation state).
  • apart from the classic presentation,  incomplete locked-in syndromes with some other residual movements exist
  • the rare total locked-in syndrome is characterized by complete loss of all voluntary motor activity, including eye movements, with unimpaired consciousness and normal or nearly normal EEG
Clinical presentation
  • the patient remains awake, as reticular formation function is preserved
  • quadriplegia results from damage to the corticospinal tract; paresis of distal cranial nerves due to lesions of the corticobulbar and corticopontine tracts, leads to anarthria and aphonia, as well as respiratory and swallowing disorders
  • the patient is unable to voluntarily control breathing and urination and defecation
  • mesencephalic oculomotor function (vertical gaze, eyelid elevation, bulbar convergence, and pupillary responses) and somatosensory and auditory pathways located in the dorsal brainstem remain unaffected
  • disorders of postural reactivity may mimic decerebrate rigidity in response to external stimuli
Etiology
  • most often due to infarcts or hemorrhages occurring in the upper pons or crus cerebri (so-called mesencephalic locked-in syndrome due to occlusion of perforators from the PCA)
  • central pontine myelinolysis
  • brainstem tumor
Differential diagnosis
  • so-called “pseudo-locked-in” syndrome can arise due to:
    • severe polyneuropathy (e.g., Chronic Inflammatory Demyelinating Polyneuropathy – CIDP)
    • neuromuscular transmission disorders (such as myasthenia gravis)
  • locked-in syndrome is characterized by the preservation of vertical eye movements in an individual who is otherwise completely paralyzed
  • communication can be established using a predefined code (e.g., looking down for ‘yes’ and looking up for ‘no’), confirming intact consciousness
  • fluctuations in vigilance, along with additional cognitive or sensory deficits, may contribute to a high rate of misdiagnosis in these cases

Lacunar syndromes

The most common are:

  • pure motor hemiparesis
  • ataxic hemiparesis – lesion in the pons
  • sensorimotor lacunar stroke – lesion of the paramedian pons
  • dysarthria and clumsy hand syndrome

→ Lacunar stroke

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Brainstem syndromes
link: https://www.stroke-manual.com/brainstem-syndromes/