Paramedian Pontine Reticular Formation Research Articles

Abstract 146: Symptomatic Basilar Stenosis Presenting as Focal Tonic Posturing and Wrong Way Eyes

Introduction A common encounter for the Vascular Neurologist assessing emergent neurological complaints is recognition of stroke mimics and stroke chameleons. Unlike mimics, stroke chameleons are presentations that masquerade as an alternative neurological entity when they are truly ischemic in nature. We present a rare case of bilateral pontine infarcts masquerading as a presumptive focal tonic seizure with gaze deviation in a patient with transient decorticate posturing and wrong way eyes secondary to symptomatic basilar stenosis. Materials/Methods Case Report Results We report a case of a 77‐year‐old gentleman with a medical history of coronary artery disease, atrial fibrillation, prior liver transplant, and B‐cell lymphoma in remission who was recently discharged from an outside facility after an episode of right‐sided hemiparesis in the context of several months of kaleidoscopic‐like vision changes where electroencephalogram (EEG) showed left temporal sharp waves. Patient subsequently presented to our emergency department (ED) with fluctuating onset of alternating laterality of facial paralysis over several days and eventually left‐sided hemiparesis. On admission, magnetic resonance imaging (MRI) of the brain showed no evidence of ischemic stroke. While in the ED, the patient had a two‐minute episode of tonic flexion contraction of the left upper extremity, leftward gaze, and intact awareness, with cessation after 2 milligrams of intravenous (IV) lorazepam. He was subsequently loaded with IV lacosamide with suspicion for focal motor seizure resulting in a post‐ictal Todd's paralysis. Follow‐up vessel imaging subsequently showed a severely stenotic basilar artery with intraluminal thrombus, raising concern of brainstem hypoperfusion. EEG the following morning was normal. On day 3, given clinical concern persisted, repeat MRI Brain revealed bilateral pontine infarcts. The patient was treated with IV heparin and blood pressure support. He was ultimately discharged ambulatory with a walker with mild facial palsy. Conclusion With much attention placed on stroke mimics in clinical practice, stroke chameleons require a high index of suspicion for the prompt identification of patients presenting with acute ischemic stroke. Brainstem ischemia warrants close attention, with decorticate posturing presenting similarly to a focal tonic motor seizure and a paramedian pontine reticular formation lesion presenting with wrong way eyes (i.e. gaze deviation towards the affected limb), exhibiting high potential for misdiagnosis. This case highlights the complexities of brainstem anatomy, places focus on the variability of the presenting features of stroke and underscores the caliber clinical suspicion carries in patients with MRI‐negative strokes.

Contraversive Ocular Tilt Reaction, Body Lateropulsion and Gaze-Evoked Nystagmus After Inferior Cerebellar Peduncle and Dentate Nucleus Stroke

Contraversive Ocular Tilt Reaction, Body Lateropulsion and Gaze-Evoked Nystagmus After Inferior Cerebellar Peduncle and Dentate Nucleus Stroke

Pons Lezyonlarının İki Nadir Prezentasyonu: Bir Buçuk Ve Sekiz Buçuk Sendromu

One-and-a-half syndrome refers to a unilateral lesion involving the ipsilateral medial longitudinal fascicle and the 6th cranial nevre nucleus and/or the paramedian pontine reticular formation. Eight-and-a-half syndrome is a syndrome in which one-and-a-half syndrome and ipsilateral 7th cranial nevre palsy are seen together. These rare conditions result from limited lesions of the pontine tegmentum. We presented two cases with one-and-a-half and eight-and-a-half syndromes with ischemic infarction and hemorrhage in pons, respectively.

A case of cardioembloic stroke with wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome

Here, we report a case of an 85-year-old man who presented sudden onset of diplopia, dysarthria, and gait disturbance. On admission, he exhibited bilateral adduction palsy, convergence palsy, and binocular exotropia in the forward gaze showing wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome. He had a history of chronic nonvalvular atrial fibrillation. DWI-MRI revealed acute ischemic lesions in the paramedian pontine tegmentum, lower midbrain, both cerebellar hemispheres, and left frontal cortex. He was thus diagnosed with an acute phase of cardioembolic stroke. Subsequently, the right eye adduction palsy in the forward gaze was slightly improved, but other eye movement disorders persisted during discharge from the hospital. The pathology was suspected to involve bilateral damages to both medial longitudinal fasciculus and the paramedian pontine reticular formation. WEBINO syndrome was not only ascribed to lacunar infarction and large artery atherosclerosis but also cardioembolic stroke. The presence of other non-eye symptoms and multiple ischemic lesions could be the characteristics of WEBINO syndrome following cardioembolic stroke.

Histomorphological Study of The Pons and Medulla Oblongata of African Striped Group Squirrel (Xerus erythropus)

The study was undertaken to investigate the histological and functional relationships between the pons and Medulla Oblongata of African Striped Ground Squirrel (Xerus erythropus). Twenty (20) adult African striped ground squirrels were divided in to two groups: 10 males and 10 females. The ground squirrels were obtained from the surrounding villages of Zaria Local Government, Kaduna State Nigeria. Each Squirrel was euthanized using ketamine hydrochloride at dose 80mg/kg BW followed by gentle perfusion with neutral formal saline. A pair of scissors, chisel and scalpel blade was used to gently extract the brain (craniotomy). The extracted brain was fixed in bouins solution for 24hours and processed histologically. The pons and medulla are composed of conspicuous nucleus abducens, nucleus facialis and nucleus trigeminal. The nucleus facialis was found dorsal to the paramedian pontine reticular formation as group of large multipolar neurons. A conspicuous nucleus abducens was found as clusters of medium neurons located lateral to the trigeminal nucleus. In myelencephalon, the cuneate fascicles, intermediate sulcus and lateral sulcus were not evident on dorsal surface but there were grossly visible pyramids and olivary prominence on the ventral surface. Similarly, the nucleus olivary were prominent, nucleus cochlearis and spinal nucleus trigemini were well developed, nucleus hypoglossi, raphe obscurus, lateral reticular nucleus, gigantocellular reticular nucleus were all very distinct. In conclusion, the presence of distinct nuclei in the pons and medulla oblongata gives squirrels fine voluntary skills with good motor coordination and balance and good visual acuity for improved diurnal adaptation.

A-55 Neuropsychological Findings Associated with Progressive Lesion Development in Cerebral Cavernous Malformation Secondary to PDCD10 Mutation

Abstract Objective A rare mutation in the PDCD10 gene causes cerebral cavernous malformations, which can result in multiple brain hemorrhages and hundreds of lesions. Up to 50% of individuals with the PDCD10 mutation remain symptom-free throughout their lives; however, others can suffer from seizures or focal neurologic deficits. Participant: A 67-year-old Caucasian male presented for a neuropsychological re-evaluation (2020) following a progressive decline in his memory and attention dating back 20 years. A baseline neuropsychological evaluation was obtained 7 years ago. Relevant medical history included a 5 mm left falcine meningioma, epilepsy, obstructive sleep apnea, hypertension, and type II diabetes. Neuroimaging revealed over 250 scattered lesions that had advanced over the past 7 years, particularly in the paramedian pontine reticular formation, left inferior cerebellum, and right middle frontal gyrus. Results His neurocognitive profile was marked by mild impairments in immediate verbal memory. The remainder of his cognitive profile was average. Compared to his 2013 evaluation, he showed only a minimal decline in verbal memory, but he showed slight improvements in the domains of executive functioning, visuospatial abilities, and language. Conclusion Despite the marked progression of lesions documented on current neuroimaging, aside from immediate verbal memory problems the patient’s neurocognitive functioning was relatively well-preserved. He even exhibited minor improvements within several domains. Given the patient’s current neurocognitive status, this case illustrates the importance of comprehensive neuropsychological testing in cases that would appear more severe based on neuroimaging data alone. Relatedly, progression of neuropathological disease burden on neuroimaging is not necessarily accompanied by consistent progression of neuropsychological dysfunction.

A potential new brainstem reflex: The oculoglossal phenomenon.

Background: A synchronized involuntary movement of the tongue to the same side as voluntary movements of the eyes, termed the oculoglossal phenomenon, has been observed. A description of the hypothesized pathway of this phenomenon could guide the development of a rapid clinical evaluation of the long segment of the brainstem and help facilitate further studies to establish a new reflex, if possible. The aim of this study is to describe and propose the simple concept of this pathway/phenomenon, the oculoglossal phenomenon.Methods: This is an observational study. Of a newly observe brainstem phenomenon evaluated on a subject at the National Neuroscience Institute in king Fahad Medical City (KFMC), Riyadh, Saudi Arabia. After being observed incidentally in a single patient, 60 participants were tested between January and March 2020 to confirm the presence of the phenomenon. Each subject was instructed to protrude the tongue and then move their eyes horizontally to the side. If the tongue simultaneously and involuntarily moved to the same side as the eyes, the test was deemed confirmatory. A literature review was performed, and possible anatomical pathway was proposed.Results: The oculoglossal reflex was present in most (50/60, 83.3%) of the subjects. Our proposed pathway begins at the frontal cortex, followed by a projection to the paramedian pontine reticular formation, then to the contralateral medial longitudinal fasciculus and bilaterally to the hypoglossal nuclei.Conclusion: An accurate description of this phenomenon could lead to additional studies and possibly establishing it as a legitimate reflex, thus conceivably adding a new tool in the neurological examination to evaluate the brainstem’s integrity.

They Look but Do Not See—Gaze‐Evoked Eyelid Spasm

They Look but Do Not See—<scp>Gaze‐Evoked</scp> Eyelid Spasm

Eye Movement Network Originating from Frontal Eye Field: Electric Cortical Stimulation and Diffusion Tensor Imaging.

This study investigated the networks originating from frontal eye fields (FEFs) using electric cortical stimulation and diffusion tensor imaging (DTI). Seven patients with intractable focal epilepsy, in which FEFs were identified by electrical cortical stimulation, were enrolled in this study. Electric stimulation at 50 Hz was applied to the electrodes for functional mapping. DTI was used to identify the subcortical fibers originating from the FEFs with two regions of interests (ROIs) in the FEF and contralateral paramedian pontine reticular formation (PPRF). FEFs were found in the superior precentral sulcus (pre-CS) in six patients and superior frontal gyrus (SFG) in three patients. DTI detected fibers connecting FEFs and contralateral PPRFs, passing within the internal capsule. The fibers were located close to the lateral antero-superior border of the subthalamic nucleus (STN) and medial posterior border of the globus pallidus internus (GPi). This study found the characteristic subcortical networks of the FEF. These tracts should be noted to prevent complications of deep brain stimulation (DBS) of the STN or GPi.

A case of pure bilateral horizontal gaze palsy due to multiple sclerosis

AbstractA 30‐year‐old woman presented with paresthesia in her left lower limb and blurred vision. She had bilateral horizontal gaze palsy with the absence of cranial nerve symptoms such as horizontal saccades, pursuit, and facial nerve palsy. Considering her convalescence, we speculated that her pure bilateral horizontal gaze palsy was mainly caused by disturbance in paramedian pontine reticular formation (PPRF). Pure horizontal gaze palsy may also be a characteristic feature of multiple sclerosis.

“Nine Syndrome”: A Rare Neuroophthalmological Syndrome Associated with HIV Vasculopathy

AbstractThere are many named brainstem syndromic variants of medullary infarcts among which “eight-and-a-half” syndrome is a rare condition that involves ipsilateral abducens nucleus or paramedian pontine reticular formation, ipsilateral medial longitudinal fasciculus, and adjacent facial colliculus/facial nerve. Here, we describe a new variant of brainstem syndrome, which includes the clinical features of “eight-and-a-half syndrome” with associated hemiparesis. This patient is a known case of HIV illness since 6 years on antiretroviral therapy, presented with features of “Nine” syndrome.

Brain phenotyping in Moebius syndrome and other congenital facial weakness disorders by diffusion MRI morphometry.

In this study, we used a novel imaging technique, DTI (diffusion tensor imaging)-driven tensor-based morphometry, to investigate brain anatomy in subjects diagnosed with Moebius syndrome (n = 21), other congenital facial weakness disorders (n = 9) and healthy controls (n = 15). First, we selected a subgroup of subjects who satisfied the minimum diagnostic criteria for Moebius syndrome with only mild additional neurological findings. Compared to controls, in this cohort, we found a small region of highly significant volumetric reduction in the paramedian pontine reticular formation and the medial longitudinal fasciculus, important structures for the initiation and coordination of conjugate horizontal gaze. Subsequently, we tested if volume measurements from this region could help differentiate individual subjects of the different cohorts that were included in our study. We found that this region allowed discriminating Moebius syndrome subjects from congenital facial weakness disorders and healthy controls with high sensitivity (94%) and specificity (89%). Interestingly, this region was normal in congenital facial weakness subjects with oculomotor deficits of myopathic origin, who would have been classified as Moebius on the basis of purely clinical diagnostic criteria, indicating a potential role for diffusion MRI morphometry for differential diagnosis in this condition. When the entire Moebius syndrome cohort was compared to healthy controls, in addition to this 'landmark' region, other areas of significantly reduced volume in the brainstem emerged, including the location of the nuclei and fibres of cranial nerve VI (abducens nerve), and fibres of cranial nerve VII (facial nerve), and a more rostral portion of the medial longitudinal fasciculus. The high sensitivity and specificity of DTI-driven tensor-based morphometry in reliably detecting very small areas of volumetric abnormality found in this study suggest broader applications of this analysis in personalized medicine to detect hypoplasia or atrophy of small pathways and/or brainstem nuclei in other neurological disorders.

Complete horizontal gaze palsy due to bilateral paramedian pontine reticular formation involvement as a presentation of multiple sclerosis: a case report

BackgroundDemyelinating central nervous system diseases include several disorders that multiple sclerosis (MS) is identified as the most common among them. Ocular movement disturbances are a typical presentation in MS patients where lesions affect the complex and interconnected pathways involved in eye motion. Centers for gaze control are located in the pons primarily; therefore, lesions involving these centers can be presented with abnormalities in gaze. However, bilateral lesions in pontine gaze centers are exceptionally rare.Case presentationA 16-year-old girl with bilateral horizontal gaze palsy was referred to the neurology clinic. Magnetic resonance imaging of the patient indicated bilateral hyperintensities in the pons at the level of the paramedian pontine reticular formation. The patient was diagnosed with multiple sclerosis with respect to clinical and imaging findings and managed.ConclusionOcular movement abnormalities are a commonly encountered manifestation in patients with multiple sclerosis, however, bilateral gaze palsy is an exceptionally rare sign and should guide the physician to contemplate for anticipated lesions in the pons, and suspect MS, especially in childbearing-aged women. Although an extensive workup should also be done to rule out possible mimickers.

Fisher one-and-a-half syndrome due to a bulb protuberance cavernoma

Abstract The one and a half Fisher syndrome is produced by a unilateral lesion in the dorsal and inferior part of the pons located specifically in the pontine tegmentum. This is an area that contains the medial longitudinal fasciculus (LMF), the paramedian pontine reticular formation (PPRF) and the nucleus of the sixth cranial nerve, responsible for the horizontal movements of the gaze. Clinically it manifests with conjugate gaze palsy with internuclear ophthalmoplegia. The case is reported on a 60 year-old patient, who presented with binocular diplopia, ophthalmoplegia and paralysis of the gaze conjugated to the left. Imaging studies were performed that showed a hemi-protuberant hematoma secondary to a cavernoma. As expected, he presented with several episodes of re-bleeding with clinical worsening: headache, diplopia, tetraparesis, and hypoaesthesia in the right side of the face, as such that the microsurgical exeresis of the protuberant cavernoma was considered.

A case report of the rare fifteen-and-a-half syndrome

Rationale:The dorsal tegmentum of the caudal pons, including the medial longitudinal fasciculus (MLF), the paramedian pontine reticular formation (PPRF), abducens nucleus, and the adjacent facial nerve is the anatomical basis of the the fifteen and a half syndrome (15½) syndrome. No patients of 15½ Syndrome presenting with bilateral peripheral facial paralysis and one-and-a-half simultaneously at the onset have been reported up to now.Patient concerns:A 54-year-old woman complained of diplopia, slurred speech, and slightly distal numbness of the left upper limb for 4 days in our hospital.Diagnoses:The diffusion weighted image (DWI) and apparent dispersion coefficient (ADC) of MRI revealed the causative lesion in pons including bilateral pontine tegmentum and a narrow lesion along the midline in the right of the pons. Her clinical manifestations with results of MRI resulted in the diagnosis of the fifteen-and-a-half-syndrome.Interventions:The patient received antiplatelet aggregation, plaque stabilization, free radicals elimination, circulation improvement, nerves nourishment, and other symptomatic treatments.Outcomes:Two months later, her ocular movement recovered, and the bilateral facial paresis showed some improvement.Lessons:First, our patient with 15½ syndrome maybe one of mutants whose bilateral pontine tegmentum is supplied by unilateral pontine paramedian perforator artery. Second, DWI combined with ADC may be applied in the diagnosis of fifteen-and-half syndrome when the lesions of infarction are too small to be revealed by MRI scan.

Síndrome del uno y medio de Fisher a causa de un cavernoma bulbo-protuberancial

The one and a half Fisher syndrome is produced by an unilateral lesion in the dorsal and inferior part of the pons located specifically in the pontine tegmentum. This is an area that contains the medial longitudinal fasciculus (LMF), the paramedian pontine reticular formation (PPRF) and the nucleus of the sixth cranial nerve, responsible for the horizontal movements of the gaze. Clinically it manifests with conjugate gaze palsy with internuclear ophthalmoplegia.The case is reported on a 60 year-old patient, who presented with binocular diplopia, ophthalmoplegia and paralysis of the gaze conjugated to the left. Imaging studies were performed that showed a hemi-protuberant haematoma secondary to a cavernoma. As expected, he presented with several episodes of re-bleeding with clinical worsening: headache, diplopia, tetraparesis, and hypoaesthesia in the right side of the face, as such that the microsurgical exeresis of the protuberant cavernoma was considered.

Ocular dipping movements in an electrocution cardiac arrest survivor

Background : Abnormal eye movements can occur in patients with neurological diseases. These have been described in unconscious patients due to anoxic coma and often disappear as the patient regains consciousness. Ocular dipping movements are rarely seen in practice in pediatric patients. Methods : A one year old male patient was brought unconscious with electrocution injury. With resuscitation, he became hemodynamically stable. He could not recognize his mother or respond to visual/auditory stimuli; and had generalized hypertonia. Cranial nerves were normal. He showed abnormal involuntary conjugate vertical saccadic eye movements, consisting of slow downward movement (for 1-2 seconds) followed by a relatively faster return to the primary mid-position. These persisted continuously for 48 hours at irregular intervals of 1-2 seconds. The patient was awake but non-responsive and not interested in surroundings. Results : These eye movements are called ocular dipping (OD) . In a normal person, saccadic movements are meant for stable fixation and are maintained by pause-cell neurons positioned in the pontine raphe. These prevent the occurrence of unwanted saccadic pulses by inhibiting the saccadic premotor burst neurons in the paramedian pontine reticular formation and midbrain. Injury to pause cells leads to extraneous saccades without fixation. It appears that cortical and basal ganglia malfunction causes ocular dipping. OD is mainly seen in anoxic coma and creuztfelt Jacob disease. A 53-year-old man developed ocular dipping following prolonged hypotension.Our patient was in vegetative state with normal respiratory and cardiac function suggesting that major midbrain and medullary centers were intact. Conclusion : The self limiting nature of OD suggests that these are caused by diffuse dysfunction rather than a single structural locus.

Delineating function and connectivity of optokinetic hubs in the cerebellum and the brainstem.

Optokinetic eye movements are crucial for keeping a stable image on the retina during movements of the head. These eye movements can be differentiated into a cortically generated response (optokinetic look nystagmus) and the highly reflexive optokinetic stare nystagmus, which is controlled by circuits in the brainstem and cerebellum. The contributions of these infratentorial networks and their functional connectivity with the cortical eye fields are still poorly understood in humans. To map ocular motor centres in the cerebellum and brainstem, we studied stare nystagmus using small-field optokinetic stimuli in the horizontal and vertical directions in 22 healthy subjects. We were able to differentiate ocular motor areas of the pontine brainstem and midbrain in vivo for the first time. Direction and velocity-dependent activations were found in the pontine brainstem (nucleus reticularis, tegmenti pontis, and paramedian pontine reticular formation), the uvula, flocculus, and cerebellar tonsils. The ocular motor vermis, on the other hand, responded to constant and accelerating velocity stimulation. Moreover, deactivation patterns depict a governing role for the cerebellar tonsils in ocular motor control. Functional connectivity results of these hubs reveal the close integration of cortico-cerebellar ocular motor and vestibular networks in humans. Adding to the cortical concept of a right-hemispheric predominance for visual-spatial processing, we found a complementary left-sided cerebellar dominance for our ocular motor task. A deeper understanding of the role of the cerebellum and especially the cerebellar tonsils for eye movement control in a clinical context seems vitally important and is now feasible with functional neuroimaging.

Reticular Formation Connections Underlying Horizontal Gaze: The Central Mesencephalic Reticular Formation (cMRF) as a Conduit for the Collicular Saccade Signal.

The central mesencephalic reticular formation (cMRF) occupies much of the core of the midbrain tegmentum. Physiological studies indicate that it is involved in controlling gaze changes, particularly horizontal saccades. Anatomically, it receives input from the ipsilateral superior colliculus (SC) and it has downstream projections to the brainstem, including the horizontal gaze center located in the paramedian pontine reticular formation (PPRF). Consequently, it has been hypothesized that the cMRF plays a role in the spatiotemporal transformation needed to convert spatially coded collicular saccade signals into the temporally coded signals utilized by the premotor neurons of the horizontal gaze center. In this study, we used neuroanatomical tracers to examine the patterns of connectivity of the cMRF in macaque monkeys in order to determine whether the circuit organization supports this hypothesis. Since stimulation of the cMRF produces contraversive horizontal saccades and stimulation of the horizontal gaze center produces ipsiversive saccades, this would require an excitatory cMRF projection to the contralateral PPRF. Injections of anterograde tracers into the cMRF did produce labeled terminals within the PPRF. However, the terminations were denser ipsilaterally. Since the PPRF located contralateral to the movement direction is generally considered to be silent during a horizontal saccade, we then tested the hypothesis that this ipsilateral reticuloreticular pathway might be inhibitory. The ultrastructure of ipsilateral terminals was heterogeneous, with some displaying more extensive postsynaptic densities than others. Postembedding immunohistochemistry for gamma-aminobutyric acid (GABA) indicated that only a portion (35%) of these cMRF terminals are GABAergic. Dual tracer experiments were undertaken to determine whether the SC provides input to cMRF reticuloreticular neurons projecting to the ipsilateral pons. Retrogradely labeled reticuloreticular neurons were predominantly distributed in the ipsilateral cMRF. Anterogradely labeled tectal terminals were observed in close association with a portion of these retrogradely labeled reticuloreticular neurons. Taken together, these results suggest that the SC does have connections with reticuloreticular neurons in the cMRF. However, the predominantly excitatory nature of the ipsilateral reticuloreticular projection argues against the hypothesis that this cMRF pathway is solely responsible for producing a spatiotemporal transformation of the collicular saccade signal.

One and a half syndrome following penetrating head injury: Case report

The authors report a case of a 22-year-old otherwise healthy female who presented following a head injury during a bar altercation, with no associated loss of consciousness and an unknown mechanism of injury. Examination revealed an isolated 1cm laceration on the right upper eyelid, superior to her medial canthus. She experienced diplopia on right horizontal gaze due to a left internuclear ophthalmoplegia (INO) with an associated left conjugate horizontal gaze palsy, collectively described as a left one-and-a-half syndrome. CT and MRI demonstrated evidence of a deep penetrating injury above the right medial canthus, traversing the ethmoid and sphenoid sinuses, the dorsum sella, narrowly missing the basilar artery, penetrating the pons, and extending to the floor of the contralateral fourth ventricle. The patient was diagnosed with multiple sinus fractures, lesions in her left paramedian pontine reticular formation (PPRF) and medial longitudinal fasciculus (MLF), and progressive pneumocephalus. She underwent a transsphenoidal endoscopic repair via a vascularized mucosal flap without complication. Postoperatively, the patient’s pneumocephalus resolved and her conjugate gaze markedly improved; however, minimal diplopia remained. This case demonstrates the importance of the clinical exam, and its benefit in localizing imaging findings and guiding treatment.