Journal of Neurology

, Volume 256, Issue 6, pp 898–903 | Cite as

Classical crossed brain stem syndromes: myth or reality?

Original Communication

Abstract

Numerous crossed brain stem syndromes have been described, especially in the nineteenth century. While these syndromes are passed on in neurological textbooks, their relevance in clinical neurology remains to be elucidated. To investigate the prevalence of classical crossed brain stem syndromes in clinical practice, we prospectively recruited 308 consecutive patients with signs and symptoms indicative of acute brain stem infarction. Standardized high-resolution MR imaging and multimodal electrophysiological brain stem testing were applied to localize the site of the acute lesion. We performed a computer-based correlation of clinical signs and symptoms of our patients to those reported in the original historical publications for more than 25 crossed brain stem syndromes. Fourteen cases matched the clinical criteria of Wallenberg’s syndrome, two patients had Babinski-Nageotte’s syndrome, two had Raymond-Cestan’s, one showed Weber’s, and one Claude’s syndrome. All other tested syndromes were not present in the cohort. More than 20% of patients showed different, so far unnamed crossed symptom combinations. In conclusion, except for Wallenberg’s syndrome, classical crossed brain stem syndromes do not seem to play a relevant role in clinical neurology. Other syndromes may serve as theoretical models only that illustrate possible neuroanatomical connections in the human brain stem. This is complicated, however, by considerable topographic and terminological inconsistencies.

Keywords

History of neurology Neuroepidemiology Brain stem Cerebrovascular disease MRI 

Background

A considerable variety of crossed brain stem syndromes has been described in the neurological literature, especially in the nineteenth century. Most of these syndromes comprise ipsilateral cranial nerve lesions and contralateral signs of long tract involvement, such as hemiparesis or a hemisensory deficit. More than 25 corresponding syndromes have been named according to their first describer so far. They are usually used as eponyms to characterize a complex neurological state like in the classical case of Wallenberg’s syndrome [17]. While hardly anything is known about the prevalence of these syndromes, definitions in modern neurological literature are often inaccurate and show growing topodiagnostic as well as terminological inconsistencies [4, 7, 13]. It is even debated whether some of these syndromes actually exist at all as a correlate of brain stem dysfunction [5]. Nevertheless, the majority of these eponyms are repeatedly cited in neurological textbooks and even in modern neurological literature.

In order to investigate the prevalence and clinical relevance of a variety of brain stem syndromes, we performed a computer-based analysis of symptom distribution in more than 300 prospectively recruited patients with acute signs of brain stem ischemia at an academic neurological center with a long tradition of anatomical/structural brain stem mapping.

Patients and methods

Over a 3-year period, we prospectively recruited 308 consecutive patients with acute signs and symptoms of vertebrobasilar ischemia. We rated acute ocular motor disorders, cranial nerve lesions and limb, trunk, stand or gait ataxia as indicators of vertebrobasilar dysfunction.

Approval of the study was granted by the university ethics committee, and patients gave informed consent to the procedures.

Clinical investigation

A detailed clinical investigation was done within 24 h after onset of symptoms using standard clinical procedures with a focus on ocular motor disorders, cranial nerve lesions or signs of long tract involvement like pyramidal tract lesions, lemniscal or pain/temperature sensory deficits, hemiataxia or lateropulsion. All signs and symptoms were entered in a specially designed ACCESS database for further statistical analysis.

The patient had to fulfill all cited criteria for a positive match with the syndromes according to their historical description (Table 3). Only for the more extensive medullary syndromes of Babinski-Nageotte, Wallenberg, and Reinhold was one missing ipsilateral clinical sign accepted.

Electrophysiological investigations

For detailed assessment of brain stem dysfunction, a battery of functional electrophysiological brain stem testing was applied in all patients in whom the clinical condition allowed functional testing. This comprised brain stem reflexes (blink reflex, jaw jerk, masseter inhibitory reflex), auditory evoked potentials (AEPs), and electrooculography with caloric stimulation. Electrophysiological testing was used to prove a functional brain stem lesion in patients with normal MRI, but with clinical rating of brain stem ischemia as the best final diagnosis.

MR imaging

Biplanar T2- and diffusion-weighted (DWI) MRI was done within 48 h after onset of symptoms with a 1.5-T superconducting system (Magnetom Vision, Siemens, Erlangen, Germany). We used DW-echo planar imaging with separately applied diffusion gradients in the three spatial axes to prove the acuity of the lesion. Axial and sagittal high-resolution T2/T1-weighted imaging before and after intravenous gadolinium was done as soon as patients could tolerate the longer lasting MRI scan (median 6.5 days after onset of symptoms). To ensure standardized imaging, slice orientation was parallel (sagittal sections) and perpendicular (axial sections) to the sagittal brainstem cuts of the stereotactic anatomical atlas of Schaltenbrand and Wahren [12].

Results

Patient data

MR imaging was impossible in 27 of the 308 patients with clinical signs and symptoms indicative of vertebrobasilar ischemia due to claustrophobia, the clinical condition or metal implants. In 36 of the remaining patients, MRI or further investigations revealed a diagnosis other than brain stem infarction: pure cerebellar ischemia (14), tumor (3), vestibular neuritis (6), inflammatory disease (6), or others (7). In the remaining 245 patients an acute brain stem ischemia was rated as the best final diagnosis according to clinical investigation, MRI, and electrophysiological brain stem testing. Of the 245 patients, 189 (77.1%) showed an acute brain stem infarction in MRI. Lesion location was mesencephalic in 18 patients (9.5%), pontomesencephalic in 34 (18.0%), pontine in 69 patients (36.5%), pontomedullary in 32 (16.9%), and medullary in 36 cases (19.0%). Fourteen patients (7.4%) had multiple acute vertebrobasilar infarcts. In 56 (22.9%) of the 245 patients, the diagnosis of an acute brain stem lesion was based on the results of functional testing alone, while MRI failed to show the expected brain stem ischemia. Electrooculography (26.2%) and the jaw jerk (22.8%) were the functional tests most frequently affected. See Table 1 for the number of pathological findings in serial electrophysiological investigations.
Table 1

Pathological findings in serial electrophysiological tests

Test

Pathological findings

Electrooculography

52/198 (26.2%)

Jaw jerk

49/215 (22.8%)

Blink reflex

40/208 (19.2%)

Masseter inhibitory reflex

38/215 (17.7%)

Auditory evoked potentials

21/221 (9.5%)

In 214 of these patients a complete diagnostic workup was available. Sonography and MR-angiography detected occlusion or stenosis of a vertebral artery in 46 patients (21.5%). Four patients had a vertebral artery dissection, in two cases following a chiropractic maneuver. Seventy-one patients (33.2%) had multiple vascular risk factors, and sonography demonstrated atherosclerosis of the extracranial arteries, but no vertebral artery stenosis or occlusion. Forty-three patients (20.1%) had cardioembolic infarction due to atrial fibrillation or a patent foramen ovale with combined atrial septal aneurysm. Two patients had Wegner’s granulomatosis. In 48 patients (22.4%), the etiology of the infarction remained unclear.

The most common clinical sign was gait ataxia in 60.8% of the 245 patients. Ipsilateral cranial nerve lesions were present in 18.8% of patients, while the most common cranial nerve deficit was that of the 5th nerve (11.4%). Motor hemiparesis was the most common long tract sign contralateral to lesion location (21.6%). See Table 2 for further clinical characteristics. According to the computer-based symptom mapping analysis, 14 cases matched the clinical criteria of Wallenberg’s syndrome, 2 patients had Babinski-Nageotte’s syndrome, 2 had Raymond-Cestan’s, 1 Weber’s and 1 Claude’s syndrome. See Tables 3 and 4 for more detailed clinical data in the 19 patients matching one of the crossed brain stem syndromes.
Table 2

Clinical signs in patients with brain stem ischemia (n = 245)

Gait ataxia

149 (60.8%)

Dysarthria

55 (22.4%)

Nystagmus

42 (17.1%)

Skew deviation

24 (9.8%)

Ipsilateral

 Cranial nerve lesion

46 (18.8%)

  5th nerve

28 (11.4%)

  6th nerve

11 (4.5%)

  7th nerve

8 (3.3%)

 Internuclear ophthalmoplegia

27 (11.0%)

Contralateral

 Motor hemiparesis

53 (21.6%)

 Hemiataxia

25 (10.2%)

 Sensory deficit pain/temperature

32 (14.3%)

 Sensory deficit light touch

18 (7.3%)

Table 3

Prevalence of crossed brain stem syndromes according to the computer-based mapping analysis

Syndrome name

Ipsilesional

Contralesional

No.

Mesencephalon

 Benedikt

3rd nerve palsy

Hemiataxia

Hyperkinesia

Rigor

0

 Claude

3rd nerve palsy

Hemiataxia

1

 Weber

3rd nerve palsy

Hemiparesis

1

 Nothnagel

3rd nerve palsy

Hemiataxia

Ptosis

M. rectus superior paresis

0

Pons

 Grenet

Trigeminal deficit

Hemihypalgesia

Hemithermhypaesthesia

0

 Gasperini

Trigeminal deficit

7th nerve palsy

Gaze palsy

Hemihypaesthesia

0

 Raymond-Cestan

Gaze palsy

Hemiataxia

Hemiparesis

Hemihypaesthesia

2

 Raymond

6th nerve palsy

Hemiparesis

0

 Millard-Gubler

6th nerve palsy

7th nerve palsy

Hemiparesis

0

 Brissaud-Sicard

Facial spasm

Hemiparesis

0

 Foville (superior)

6th nerve palsy

Hemiparesis

Hemihypaesthesia

0

 Foville (inferior)

6th nerve palsy

7th nerve palsy

Hemiparesis

Hemihypaesthesia

 

 Pierre-Marie-Foix

6th nerve palsy

7th nerve palsy

Horner’s syndrome

Hemiparesis

Hemihypaesthesia

0

 Gellé

Hypakusis/tinnitus

Vertigo

Hemiparesis

0

Medulla oblongata

 Babinski-Nageotte

Trigeminal deficit

Horner’s syndrome

Hemiataxia

Vail paresis

Vocal cord paresis

Hemiparesis

Hemihypalgesia

Hemithermhypaesthesia

2

 Wallenberg

Trigeminal deficit

Horner’s syndrome

Hemiataxia

Vail paresis

Vocal cord paresis

Hemihypalgesia

Hemithermhypaesthesia

14

 Cestan-Chenais

Trigeminal deficit

Horner’s syndrome

Vail paresis

Vocal cord paresis

Hemiparesis

Hemihypalgesia

Hemithermhypaesthesia

0

 Reinhold

Trigeminal deficit

Horner’s syndrome

Vail paresis

Vocal cord paresis

Hemiataxia

Hypoglossal paresis

Hemiparesis

Hemihypalgesia

Hemithermhypaesthesia

Hemihypaesthesia

0

 Avellis

Vail paresis

Vocal cord paresis

Hemiparesis

Hemihypaesthesia

0

 Schmidt

Vail paresis

Vocal cord paresis

11th nerve palsy

12th nerve palsy

Hemiparesis

0

 Tapia

Vail paresis

Vocal cord paresis

12th nerve palsy

Hemiparesis

0

 Vernet

Vail paresis

11th nerve palsy

Hemiageusia posterior tongue

Pharyngeal hemihypaesthesia

Hemiparesis

0

 Jackson

Vail paresis

Vocal cord paresis

12th nerve palsy

Hemiparesis

0

 Dejerine

12th nerve palsy

Hemiparesis

0

 Spiller

12th nerve palsy

Hemiparesis

Hemihypaesthesia

0

Table 4

Clinical characteristics in patients matching crossed brain stem syndromes

Patient

Syndrome

Missing signs

Additional signs

Additional lesion

Aetiology

1

Wallenberg

 

Facial weakness

Cerebellum

VA dissection

2

Wallenberg

Vail paresis

  

RF, AS

3

Wallenberg

   

Unclear

4

Wallenberg

Vocal cord paresis

  

Cardioembolic

5

Wallenberg

   

VA occlusion

6

Wallenberg

Horner’s sign

  

Wegener’s disease

7

Wallenberg

 

Facial weakness

 

VA occlusion

8

Wallenberg

 

Skew deviation

 

Unclear

9

Wallenberg

  

Cerebellum

VA occlusion

10

Wallenberg

  

Cerebellum

Cardioembolic

11

Wallenberg

 

Facial weakness

 

Unclear

12

Wallenberg

  

Cerebellum

Cardioembolic

13

Wallenberg

Vail paresis

Skew deviation

 

RF, AS

14

Wallenberg

Horner’s sign

 

Cerebellum

Cardioembolic

15

Babinski-Nageotte

Vocal cord paresis

  

RF, AS

16

Babinski-Nageotte

  

Cerebellum

VA occlusion

17

Raymond-Cestan

   

Unclear

18

Raymond-Cestan

Vail paresis

  

VA stenosis

19

Claude

   

RF, AS

VA vertebral artery, RF vascular risk factors, AS atherosclerosis

When regarding symptom combinations apart from described crossed brain stem syndromes, the most frequent syndromes in our cohort were gait ataxia combined with hemiataxia (15.1%) and gait ataxia with dysarthria (6.5%) as typical signs in dorsal/lateral medullary infarctions. Moreover, dysarthria combined with motor hemiparesis (8.6%) was a frequent correlate of ventral pontine ischemia. When regarding crossed syndromes, trigeminal deficits combined with hemiataxia (7.8%), or impaired contralateral pain/temperature sensation (4.9%), as well as Horner’s syndrome combined with contralateral hemiataxia (6.5%) or impaired pain/temperature sensation (4.5%) were frequent symptom combinations, all typical in dorsal/lateral medullary infarction.

Discussion

According to our findings, only Wallenberg’s syndrome seems to be of clinical importance, whereas the remaining classical crossed brain stem syndromes are missed in clinical practice (Fig. 1). Some others may occur occasionally, such as the syndromes of Weber, Claude, Raymond-Cestan, and Babinski-Nageotte. Even in Wallenberg’s syndrome, nearly half of our patients did not fulfill all symptoms described by Wallenberg or had additional symptoms of brain stem dysfunction [17]. Wallenberg’s syndrome is a clinical correlate of classical lateral medullary infarction, which is a frequent area of ischemia due to the vascular architecture of the brain stem [2].
Fig. 1

Typical lateral medullary lesion in patient 4 with Wallenberg’s syndrome (a) and in patient 15 with Babinski-Nageotte syndrome (b), transversal T2-weighted image

Most of the crossed brain stem syndromes have been described in the nineteenth and few in the early twentieth century on the basis of single case studies, sometimes with correlation to autopsy findings. At that time, imaging of the central nervous system or elaborate functional testing was not available to prove the suspected acute brain stem lesion in vivo. While these syndromes are generally cited in textbooks on clinical neurology and in modern literature, several of the eponyms used in clinical diagnosis today do not exactly correspond to the first descriptions of the nineteenth century anymore. Investigations on the prevalence of these syndromes and their growing terminological inconsistencies are rare. Corresponding publications are mainly published in German language, and their access is limited [4, 5, 13]. Over the decades, syndromes have been simplified or have been extended by terms like “Wallenberg-plus” [11]. Parinaud’s syndrome is often used as a synonym for a dorsal midbrain syndrome, which does not correspond to the original description [10, 13]. Modern citations of the Avellis syndrome do not correspond to the historical description of the crossed medullary syndrome [1], while other syndromes like those of Foville or Millard-Gubler are occasionally mixed up with each other in the literature [3, 6, 9, 15]. Moreover, some syndromes have probably never been described by the authors to whom they are attributed. This applies for example to the syndromes that are attributed to Gasperini or to Grenet [6]. Other syndromes, like those of Schmidt [14] or Vernet [16], have actually never been described as a correlate of a brain stem lesion and probably represent multiple cranial nerve lesions instead [5].

All these limitations restrict the clinical value of the historical crossed brain stem syndromes in neurological practice. Moreover, according to our data, most of the syndromes do not exist at all in clinical practice, even at specialized academic neurological centers. Other crossed syndromes like that of an ipsilateral trigeminal deficit combined with a pure contralateral hemiataxia are far more frequent, but have never been named accordingly. To the best of our knowledge, this is the largest prospectively recruited unselected cohort of patients with brain stem infarctions. Our investigation is limited in that it is based on ischemic brain stem lesions alone. Brain stem ischemia is, however, by far the most frequent cause of acute brain stem lesions, and most of the cited syndromes have been initially described as a sequel of brain stem infarction. Tumors in the posterior fossa are rare, and brainstem lesions in inflammatory diseases are usually multitopic and thus unsuitable for topographic studies in oligosymptomatic syndromes. According to earlier investigations, routine MR imaging is able to detect only about 80% of functional brain stem lesions [8]. Therefore, we included a broad battery of electophysiological brain stem tests to prove a central brain stem affection in our patients with acute vertebrobasilar symptoms. Another drawback of our study is the fact that the mechanisms of ischemia were multiplex in our cohort, whereas most of the named brainstem syndromes are penetrator syndromes or territorial infarcts involving several penetrating arteries. This cohort does, however, represent clinical practice as it is based on consecutive patients prospectively recruited over a 3-year period of time.

In conclusion, crossed brain stem syndromes other than Wallenberg’s syndrome do not seem to have a major clinical importance. They may serve as theoretical constructs illustrating the functional neuroanatomy of the brain stem for educational purposes. This is, however, considerably complicated by multiple terminological and topographic inconsistencies when regarding the historical descriptions.

Notes

Acknowledgments

The study was supported by the DFG (Deutsche Forschungsgemeinschaft: Ho293/10-2).

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Department of NeurologyJohannes Gutenberg-University MainzMainzGermany

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