A new method to investigate brain stem structural–functional correlations using digital post-processing MRI – reliability in ischemic internuclear ophthalmoplegia

We investigated the reliability of a new digital post-processing magnetic resonance imaging (MRI) technique in ischemic brain stem lesions to identify relations of the lesion to anatomical brain stem structures. The target was a medial longitudinal fasciculus (MLF) lesion, which was evident from ipsilateral internuclear ophthalmoplegia (INO). Sixteen patients with acute unilateral INO and an isolated acute brain stem lesion in T2- and EPI-diffusion weighted MRI within 2 days after the onset of symptoms were studied. The MRI slice direction was parallel and perpendicular to a slice selection of a stereotactic anatomical atlas. The individual slices were normalized and projected in the digitalized atlas. The eye movement disorder was monitored by electro-oculography. In all patients with clinical or subclinical electro-oculographically documented INO and MRI proven brain stem infarction the lesion covered or at least partially overlapped the ipsilateral MLF at one or more atlas levels. We conclude that digital post-processing MRI with normalizing and projecting brain stem lesions in an anatomical atlas is a reliable method to demonstrate the anatomical structures involved by the lesion. Combined with electrophysiological brain stem testing, this method may be a useful tool to identify incompletely understood pathways mediating brain stem reflexes or the generators of evoked potentials.     

Course and distribution of facial corticobulbar tract fibres in the lower brain stem

The course and distribution of the facial corticobulbar tract (CBT) was examined by correlating MRI of brain stem lesions with neurological symptoms and signs including central (C-FP) or peripheral facial paresis (P-FP) in 70 patients with localised infarction of the lower brain stem. C-FP occurred more often in patients with lesions of the lower pons or upper medulla of the ventromedial brain stem. Some patients with dorsolateral infarcts of the upper medulla to the lower pons showed C-FP, mostly on the lesion side. P-FP on the side of the lesion was also seen in patients with dorsolateral involvement of the lower pons. Patients with ventromedial infarction of the brain stem showed paresis of extremities contralateral to the lesion. Specific neurological symptoms and signs such as dysphagia, vertigo, nystagmus, Horner's syndrome, ipsilateral cerebellar ataxia, and contralateral superficial sensory impairment were seen in patients with dorsolateral infarcts of the brain stem. It is hypothesised that the facial CBT descends at the ventromedial lower pons, near the corticospinal tract, mainly to the level of the upper medulla, where the fibres then decussate and ascend in the dorsolateral medulla to synapse in the contralateral facial nucleus.     

Pontine lesion in opsoclonus-myoclonus syndrome shown by MRI.

Two patients with opsoclonus-myoclonus syndrome are reported whose magnetic resonance imaging (MRI) showed brain stem lesions. Both patients developed the opsoclonus-myoclonus syndrome after an upper respiratory illness. One case had visual hallucinations during the course of illness and MRI revealed a focal lesion in the pons involving the junction of basis and tegmentum. MRI of the second case showed a focal lesion at the upper pontine tegmentum.     

Partial dorsal mesencephalic hemorrhages: report of three cases

We studied three patients with spontaneous dorsal mesencephalic hemorrhages. One patient had Parinaud's syndrome with a unilateral hemorrhage confined to the rostral tectal plate. The second patient had vertical gaze palsy, skew deviation, and bilateral Horner's syndrome due to a unilateral hemorrhage that involved the superior colliculus and extended anteriorly into the midbrain tegmentum and inferiorly to the rostral dorsal pons. The third patient had a hemorrhage in the caudal tectal plate, with bilateral fourth cranial nerve palsies, unilateral Horner's syndrome, and ataxia. There was hydrocephalus due to obstruction of the aqueduct in two patients. The patients recovered, but with some degree of disability.     

Clinical and pathologic correlates of brain stem auditory response abnormalities

Short-latency auditory evoked responses were recorded in over 100 neurologic patients. Abnormalities of each response component were correlated with postmortem or radiologic localization of different brain stem lesions. These findings suggested that waves I-VII largely reflect activity at the following levels of the auditory pathway: acoustic nerve (I), pontomedullary junction (II), caudal pons (III), rostral pons or midbrain (IV), midbrain (V), thalamus (VI), and thalamus or auditory radiation (VII). When this information was applied prospectively to the evaluation of brain stem dysfunction, response abnormalities proved useful in detecting and localizing certain lesions not revealed by other tests. Serial recordings provided information about the evolution of brain stem lesions and their response to therapy.     

Serotonergic projections to the caudal brain stem: a double label study using horseradish peroxidase and serotonin immunocytochemistry

Cells of origin of serotonergic and non-serotonergic projections to the caudal brain stem in the primate were examined using a double label technique. Following HRP injections into medullary raphe nuclei and the adjacent reticular formation double labeled cells were found in the dorsal raphe nucleus, the central superior nucleus and the ventrolateral tegmentum. Retrogradely labeled cells that did not stain for serotonin-like immunoreactivity were found primarily in the periaqueductal gray (PAG) and the mesencephalic and pontine reticular formation. The results are discussed in relation to the descending pathway(s) mediating the effects of PAG stimulation.     

Midsagittal pontomedullary brain stem section: Effects on ocular adduction and nystagmus

Oculomotor function was studied after midsagittal section of the brain stem in rhesus monkeys. After lesions that involved both the medulla and pons, there was permanent paralysis of adduction during conjugate eye movements and divergent strabismus. Analysis of the lesions indicated that activity responsible for ocular adduction had crossed the brain stem in a localized region at the level of the abducens nuclei. The adductive paralysis was probably due to interruption of axons of abducens internuclear neurons that ascend in the medial longitudinal fasciculus (MLF). In view of the functional relationship of this region to ocular adduction and its close anatomic relationship to the MLF, we propose that it be called the MLF decussation. Because the eyes beat synchronously after deep interruption of vestibular commissural fibers, the latter are not essential for the production of quick phases of nystagmus. After medullary lesions, animals had spontaneous downward nystagmus and perverted caloric nystagmus. Optokinetic after-nystagmus was lost. The perverted nystagmus appears due to unmasking of anterior canal responses, secondary to a loss of inhibitory activity that normally crosses the brain stem in the vestibular commissural system.     

Orthostatic hypotension associated with dorsal medullary cavernous angioma

Background – Orthostatic hypotension (OH) is a rare manifestation of medulla oblongata lesions that may be because of interruption of descending sympathoexcitatory axons. Aims – To illustrate the location of a medullary lesion that produced OH following resection in relationship to the location of putative sympathoexcitatory pathways. Method – A case with dorsal medullary cavernous angioma presenting with OH is described. The possible localization of lesion was compared with distribution of tyrosine hydroxylase (TH)‐immunoreactive axons in a comparable section of the medulla of a control brain. Results – The patient had marked OH after partial removal of the cavernous angioma. Biopsy confirmed the diagnosis. The magnetic resonance imaging location of the lesion overlapped that of TH‐immunoreactive axons of the medullary transtegmental tract. Conclusions – A restricted lesion of medullary lesion interrupting the catecholaminergic transtegmental tract arising from the sympathoexcitatory C1 neurons of the rostral ventrolateral medulla could result in severe OH.     

Pathological yawning as a presenting symptom of brain stem ischaemia in two patients

Two cases of brain stem stroke involving the upper pons and the ponto-mesencephalic junction presented with transient excessive pathological yawning, associated with gait ataxia and in one subject with upper limb and facial hemiparesis. A causal relation is hypothesised between the brain stem lesion and pathological yawning, possibly related to denervation hypersensitivity of a putative brain stem yawn centre. Excessive yawning may herald brain stem ischaemia.     

Diffusion-weighted magnetic resonance imaging (MRI) in acute brain stem infarction]

Diffusion-weighted magnetic resonance imaging (DWI) provides one of the earliest demonstrations of ischemic lesions. However, some lesions may be missed in the acute stage due to technical limitation of DWI. We therefore conducted the study to clarify the sensitivity of DWI to acute brain stem infarctions. Twenty-eight patients with the final diagnosis of brain stem infarction(midbrain 2, pons 9, medulla oblongata 17) who had been examined by DWI within 24 hours of onset were retrospectively analyzed for how sensitively the initial DWI demonstrated the final ischemic lesion. Only obvious(distinguishable with DWI alone without referring clinical symptoms and other informations) hyperintensity on DWI was regarded to show an ischemic lesion. Sixteen(57.1%) out of 28 patients had brain stem infarctions demonstrated by initial DWI. In the remaining 12 cases, no obvious ischemic lesion was evident on initial DWI. Subsequent MRI studies obtained 127 hours, on average after the onset showed infarction in the medulla oblongata in 11 cases and in the pons in one case. Negative findings of DWI in the acute stage does not exclude possibility of the brain stem infarction, in particulary medulla oblongata infarction.     

Topography of the catecholamine neurons in the brain stem of the human fetus: an immunohistochemical study using antibodies to tyrosine hydroxylase

Immunohistochemistry using antibodies to tyrosine hydroxylase (TH), a rate-limiting enzyme which catalyzes the initial step in the catecholamine synthesizing pathway, has been widely accepted as one of the methods for identification of catecholamine neurons in the nervous system. In the present study, we performed immunohistochemical examination to elucidate the distribution of catecholamine neurons in brain stem of human fetuses. The brain stems were obtained from 8 human fetuses (CRL: 120-275 mm, GA: 15-27 wks) 1-3 h after death following therapeutic or spontaneous abortion. They were immediately fixed with 4% paraformaldehyde in 0.1 M phosphate buffer, pH 7.4, dehydrated with graded ethanol, and embedded in paraffin. Serial 6 microns sections were cut from 7 different levels of the brain stem of each fetus. These sections were stained by peroxidase-antiperoxidase (PAP) technique using TH antisera. The TH antisera used were raised in rabbits by injecting purified TH from bovine adrenal medulla. The preparation and the specificity of TH antisera were described in detail elsewhere (Nakashima et al, 1983). Catecholamine neurons were clearly demonstrated in the brain stem of all fetuses. They could be recognized as catecholamine cell groups in the same manner as is done in experimental mammals. Among these cell groups, the catecholamine neurons showed distinct cytological features in shape and size. The distribution of catecholamine positive neurons in the brain stem was almost the same in the 8 human fetuses, and an atlas was given with anatomical explanation under the terminology of Olszewski and Baxter (1982) for the human brain stem. In the mesencephalon, a large number of catecholamine neurons lay in the nucleus substantiae nigrae, pars compacta, the nucleus paranigralis, the middle of the ventral tegmentum and the tractus tegmentalis centralis, and fewer catecholamine neurons were scattered in the other tegmental area. In addition, a group of small catecholamine neurons was located in the griseum centrale mesencephali near the aqueduct. In the pons, catecholamine neurons occurred mainly in the nucleus locus coeruleus and the nucleus subcoeruleus. A band of TH-positive neurons extended from the nucleus locus coeruleus to the dorsolateral tegmentum, and further to the roof of the fourth ventricle. Occasional catecholamine neurons were present in the area medial to the upper portion of the nucleus locus coeruleus. More caudally, a small number of catecholamine neurons were scattered in the area medial to the nervus facialis and adjacent to the nucleus facialis and the nucleus olivaris superior.(ABSTRACT TRUNCATED AT 400 WORDS)     

Anatomical atlas of the baboon''s brain in the orbito-meatal plane used in experimental positron emission tomography

An anatomical atlas has been constructed of the brain of the baboon (Papio papio) in the orbito-meatal plane (OM-plane) which is frequently used in experimental positron emission tomography (PET) investigations. The atlas comprises 12 photographic reproductions of histological brain sections separated by 2.5 mm intervals, and covers telencephalic to pontine brain stem levels. The anatomical atlas was used in analysis of some PET scan images obtained after administration of either a benzodiazepine (BZ) antagonist, (11C)-Ro 15-1788, or a dopamine D2 receptor antagonist, (76Br)-bromospiperone. Since PET camera detects radiation emitted from a slice of tissue of 15 mm thickness, each PET image corresponds to the tissue represented on six levels of the anatomical atlas. In optimal conditions, the PET image shows a pattern of receptor labelling reminiscent of anatomical structures in the atlas. Sometimes, however, the superimposition of different labelled structures yields a PET image which lacks any apparent resemblance with individual anatomical structures. In these cases, the analysis of the PET scan must rely on the anatomical atlas, as well as available data on the distribution of specific binding sites.     

Effect upon the EEG of acute injury to the brain stem activating system

The effect upon the EEG in the unanesthetized "ecéphale isolé" of acute brain stem lesions in a position to involve the ascending reticular activating system has been studied. Elimination of the bulbar segment was without marked effect. Some synchronization followed elimination of the pons, but the most pronounced and prolonged changes occurred as a result of mesencephalic transection, or of discrete injury to the midbrain tegmentum or basal diencephalon, following which the EEG activation pattern of low voltage fast activity was reduced or abolished and the cortical record became dominated by recurring bursts or spindles of high voltage slow waves like those of normal sleep or barbiturate anesthesia. Bursts could be recorded from the intralaminar and other nuclei of the thalamus and these thalamic bursts were abolished by acute decortication. Conversely, cortical bursts were abolished by acute thalamic lesions. Possible interrelations of these regions in this activity is discussed. These results offer an explanation for the clinical observation of somnolence following basal injury to the brain, and suggest that a maintained influence of the ascending brain stem activating system underlies wakefulness, while absence of this influence precipitates sleep.     

Magnetic resonance imaging in clinically isolated lesions of the brain stem.

Twenty-seven patients with an isolated brain stem syndrome, thought to be due to demyelination, were examined by magnetic resonance imaging (MRI). A brain stem lesion was identified in 25, and clinically silent lesions outside the brain stem were demonstrated in 20. MRI was more sensitive than evoked potentials in detecting brain stem and other lesions. The scan findings were compared with those in 23 patients with multiple sclerosis, who had chronic brain stem dysfunction, with particular reference to the distribution of abnormalities and the MRI characteristics of the lesions. The relaxation times, T1 and T2, of the lesions were measured by MRI. These values were seen to fall in serial studies of acute lesions, but remained unchanged in the chronic lesions. MRI may therefore allow the age of lesions to be assessed.     

The connections of the mammillary complex and the hypothalamotegmental section with the stem in the lizard brain]

Hypothalamic connections with the brain stem in lizard (Ophisaurus apodus) were studied by means of local injection of HRP and WGA-HRP into the mamillary complex and massive injections into the hypothalamotegmental area. Reciprocal direct connections were shown between the mamillary complex nuclei and hypothalamotegmental structures, on the one hand, and following structures in the brain stem, on the other hand: griseum centrale, n. parabrachialis, n. lemnisci lateralis, n. raphae and reticular formation of caudal mesencephalic tegmentum, pons and medulla oblongata. It was concluded that direct reciprocal hypothalamo-brainstem connections, as a basis for autonomic-emotional and probably nociceptive and antinociceptive reactions in mammals were formed already in reptiles.     

Auditory hallucinations in lesions of the brain stem

Since the publication by Jean Lhermitte in 1922 of his paper on hallucinosis, the peduncular type has been described as a purely visual phenomenon. However, limited brain stem lesions can give rise to analogous manifestations in the auditory field. Five cases of auditory hallucinosis are reviewed, the first four resulting from a lesion of tegmentum of pons responsible for contralateral hemi-anesthesia and homolateral facial palsy with paralysis of laterality. Central type hypoacusis and a severe disorder of localization of sounds revealed a lesion of trapezoid body. The fifth case resulted from a peduncular lesion in region supplied by superior cerebellar artery, the auditory deficit being related to a lesion of inferior corpus quadrigeminum. In one patient, the auditory hallucinosis was followed by a period of visual hallucinations and oneiric delusions. Both auditory and visual hallucinosis can be related to hypnagogic hallucinations. Dream mechanisms (the geniculo-occipital spikes system) escape from normal inhibitory control exerted by the raphe nuclei. Auditory deafferentation could predispose to auditory hallucinosis.     

Electrophysiological brain stem investigations in idiopathic narcolepsy

Narcolepsy is associated with various rapid eye movement (REM) sleep abnormalities. Distinct brain stem areas seem to play a prominent role in REM sleep regulation. Recent magnetic resonance imaging (MRI) studies have led to conflicting findings concerning the presence of structural brain stem lesions in patients with idiopathic narcoleptic syndrome. However, multimodal electrophysiological brain stem investigations may reveal functional brain stem abnormalities even in the absence of MRI abnormality. Therefore we investigated brain stem function in 12 idiopathic narcoleptic patients by systematically studying tegmental brain stem pathways. All of the patients met the diagnostic criteria of the International Classification of Sleep Disorders, with typical changes in polysomnography and the multiple sleep latency test. Electrophysiological investigations comprised masseter reflex, blink reflex, masseter inhibitory reflex, early auditory evoked potentials and electrooculography with vestibular testing. In no patient were electrophysiological brain stem abnormalities observed. Our findings do not support the existence of a relevant brain stem lesion in narcoleptic patients with normal neurological status. Received: 23 September 1997 Received in revised form: 23 January 1998 Accepted: 10 February 1998     

Direct trans-sylvian approach to the ventrolateral pons in surgical management of large cystic cavernous malformations of the brain stem in children

OBJECTIVES: In the study surgical indications are reviewed and the effect of the applied surgical technique on long-term treatment outcome in children with large cystic brainstem cavernous malformations is evaluated. METHOD: Clinical data of 5 patients treated surgically for large cystic cavernous malformations of the pons in the years 1995-2001 were retrospectively evaluated. In all the cases the transsylvian approach to the ventrolateral pons with splitting of the crus cerebri was used to reach cavernoma within the cystic cavity. The long-term follow up (mean 4.9 years) included a complete neurological examination and annual MRI studies. RESULTS: At least one hemorrhagic episode was diagnosed in all the cases, while bleeding to the pons, with clinical course mimicking that of stroke, was noted twice in 3 patients. All the episodes confirmed by MRI imaging appeared to be intralesional. The malformations ranged in size from 30 to 50 mm (mean 36.9 mm). Their most characteristic MRI features were not only the localization in the pontine structure exclusively i.e. within the natural anatomical barriers separating the pons from the midbrain and medulla, but also the growth pattern corresponding to that of brainstem benign gliomas. The patients' mean preoperative KPS score was 60 (30 to 90). Cavernous hemangiomas were totally removed in 3 out of 5 cases. One patient with partially removed lesion presented after a year recurrent hemorrhage and new neurological deficits that required a second stage surgery. In all but one case transient complications included some new cranial nerve, motor and sensory deficits that influenced the patients' immediate postoperative KPS assessment, with the mean score of 48. In a follow-up assessment at 1.5 to 7 years, a significant amelioration of both their neurological status and quality of life was found, with KPS scores from 70 to 90 (mean score 80). Annual MRI examinations showed extensive hemosiderin deposits within the pontine tissue in 3 cases of totally removed cavernous hemangiomas and this image was stable during the follow-up period. CONCLUSIONS: The findings suggest that resection of large pontine cavernomas in children is indicated in cases of symptomatic hemorrhage with lesions approaching the pial surface, or surrounded by a small margin of normal tissue. Recurrent hemorrhages are intralesional (i.e. limited to pontine structures by the natural anatomical barriers), resulting in a "cyst-like" growth of malformations mimicking that of focal neoplasms and in compression of the brain stem tissue rather than in a direct hemorrhagic insult.     

The effects of brainstem lesions on vocalization in the squirrel monkey

The present study is an attempt to find out the brain areas involved in the motor coordination of species-specific vocalization. For this purpose, high-frequency coagulations were placed in a systematic manner throughout the brainstem and posterior diencephalon in altogether 43 squirrel monkeys (Saimiri sciureus). The effect of these lesions on different call types elicited by electrical brain stimulation was studied spectrographically. It was found that bilateral destruction of the ventrolateral, ventroposterior and intralaminar thalamus, periventricular and rostral periaqueductal gray, ventral tegmental area of Tsai, nucl. interpeduncularis, nucl. ruber, anterodorsolateral midbrain tegmentum, superior and inferior colliculi, pontine gray, cerebral peduncles, medial pontine reticular formation, raphe and vestibular nuclei did not affect the acoustic structure of the calls tested. On the other hand, lesions in the ventrolateral midbrain involving the substantia nigra and overlying reticular formation, in the midbrain tegmentum just below the inferior colliculus, in the lateral pons and almost the whole medulla (minimal lesion size: 2.5 mm3) changed vocalization significantly. It is suggested that the latter areas are more or less directly involved in the motor coordination of vocalization, while the first are not.