Cranial Roots Research Articles

Peripheral nervous system involvement in SARS-CoV-2 infection: a review of the current pediatric literature.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the pathogen responsible for the pandemic health emergency declared by the World Health Organization in March 2020. During the first part of the pandemic, adults showed mild to severe respiratory symptoms. Children seemed initially exempt, both from acute and subsequent complications. Hyposmia or anosmia were promptly identified as the main symptoms of acute infection, so neurotropism of SARS-CoV-2 was immediately suspected. (1, 2). As the emergency progressed, post infectious neurological complications were described also in pediatric population (3). Cases of cranial neuropathy in connection with acute SARS-CoV-2 infection have been reported in pediatric patients, as an isolate post infectious complication or in the context of the multisystem inflammatory syndrome in children (MIS-C) (4-6). Neuroinflammation is thought to be caused by several mechanisms, among which immune/autoimmune reactions (7), but so far, no specific autoantibody has been identified. SARS-CoV-2 can enter the central nervous system (CNS) directly and/or infect it retrogradely, through the peripheral nervous system (PNS), after replicating peripherally; several factors regulate invasion and subsequent neuroinflammation. Indeed, direct/secondary entry and replication can activate CNS-resident immune cells that, together with peripheral leukocytes, induce an immune response and promote neuroinflammation. In addition, as we will discuss in the following review, many cases of peripheral neuropathy (cranial and non-cranial) have been reported during or after SARS-CoV-2 infection. However, some authors have pointed out that the increase of cranial roots and ganglia in neurological imaging is not always observed in children with cranial neuropathy. (8). Even if a variety of case reports were published, opinions about an increased incidence of such neurologic diseases, linked to SARS-CoV-2 infection, are still controversial (9-11). Facial nerve palsy, ocular movements abnormalities and vestibular alterations are among the most reported issues in pediatric population (3-5). Moreover, an increased screen exposure imposed by social distancing led to acute oculomotion's disturbance in children, not primarily caused by neuritis (12, 13). The aim of this review is to suggest food for thought on the role of SARS-CoV-2 in neurological conditions, affecting the peripheral nervous system to optimize the management and care of pediatric patients.

The Distance Between the Cranial Nerve IX-X Root Entry/Exit Zone and the Pontomedullary Sulcus: MR Imaging Study in Patients With Hemifacial Spasm

SubjectTo quantitatively describe the distance between the cranial nerve (CN) IX-X root entry/exit zone (REZ) and the pontomedullary sulcus in patients with hemifacial spasm (HFS).MethodsA total of 215 outpatients with HFS were recruited. Finally, 108 patients who yielded high-quality images were enrolled in the study. MRIs were reconstructed to measure the distance between the bilateral CN IX-X REZs and the corresponding pontomedullary sulcus.ResultsAmong the 108 patients, the ratio of males to females was 39/69, and the mean age was 57.9 ± 6.5 years. The ratio of left to right HFS involvement was 47/61. The average height was 1.62 ± 0.07 m, and the average body mass index (BMI) was 24.65 ± 2.97 kg/m2. The distance between the cephalic end of the CN IX-X REZ and the pontomedullary sulcus was 2.7 ± 0.9 mm. The distance between the caudal end of the CN IX-X REZ and the pontomedullary sulcus was 7.6 ± 1.1 mm. No monotonic relationship was found between distance and height or BMI in the scatter diagrams.ConclusionsThe CN IX-X REZ is closely related to the pontomedullary sulcus in patients with HFS, and there is no difference between the left and right sides. The distances were not correlated with height or BMI in patients with HFS.

Is Immobile vocal fold Related to the Spinal Accessory Nerve Agenesis?: A Case Report

The spinal accessory nerve innervates the sternocleidomastoid and trapezius muscles, but the internal branch from the spinal accessory nerve is also contributing to the motor innervation of the larynx. For the first time, we report a case of an impairment of sternocleidomastoid, trapezius, and thyroarytenoid muscles from the same side. In our case, the anatomical variant that can explain this situation implies the cranial roots and some fibers from the spinal roots of the spinal accessory nerve to form the internal branch. In the case of agenesis of these spinal roots, the muscles reliant on it would be missing. For this reason, it is advisable to rule out laryngeal problems in patients with sternocleidomastoid and/or trapezius muscles impairment.

The Accessory Nerve: A Comprehensive Review of its Anatomy, Development, Variations, Landmarks and Clinical Considerations.

The eleventh cranial nerve, the accessory nerve, has a complex and unique anatomy and has been the subject of much debate. Herein, we review the morphology, embryology, surgical anatomy, and clinical manifestations of the accessory nerve. Included in this review, we mention variant anatomy, molecular development, histology, and imaging of the accessory nerve. The accessory nerve continues to be a topic of much discussion regarding its exact function and in particular to its cranial roots. Recently, various surgical procedures have been devised that repurpose the accessory nerve (e.g., lengthening procedures, contralateral neurotization procedures). Currently, we continue to learn and have much to learn about this lower cranial nerve. Anat Rec, 302:620-629, 2019. © 2018 Wiley Periodicals, Inc.

Variations of the accessory nerve: anatomical study including previously undocumented findings-expanding our misunderstanding of this nerve

Introduction: The anatomy of the accessory nerve has been well described but continued new clinical and anatomical findings exemplify our lack of a full understanding of the course of this nerve. Therefore, this study aimed to expand on our knowledge of the course of the 11th cranial nerve via anatomical dissections.Methods: Fifty-six cadavers (112 sides) underwent dissection of the accessory nerve from its cranial and spinal origins to its emergence into the posterior cervical triangle. Immunohistochemistry was performed when appropriate.Results: Our findings included two cases (1.8%) where the nerve was duplicated, one intracranially and one extracranially. One accessory nerve (0.9%) was found to enter its own dural compartment within the jugular foramen. The majority of sides (80%) were found to have a cranial root of the accessory nerve. Thirty-one sides (28%) had connections to cervical dorsal roots medially and three sides (2.7%) laterally. Medial connections were most common with the C1 nerve. Medial components of these dorsal root connections were all sensory in nature. However, lateral components were motor on two sides (1.8%). Nerves traveled anterior to the internal jugular vein on 88% of sides. One (0.9%) left side nerve joined an interneural anastomosis between the dorsal rootlets. Macroganglia were found on the spinal part of the intracranial nerve on 13% of sides. The lesser occipital nerve arose directly from the accessory nerve on two sides (1.8%) and communicated with the accessory nerve on 5.4% of sides. One side (0.9%) was found to communicate with the facial nerve with both nerves innervating the sternocleidomastoid muscle.Conclusions: Additional anatomical knowledge of the variants of the accessory nerve may benefit patient care when this nerve is pathologically involved.

Functional anatomy of the accessory nerve studied through intraoperative electrophysiological mapping.

OBJECTIVE Classically the 11th cranial nerve (CN XI, or accessory nerve) is described as having a cranial and a spinal root, the latter arising from the upper segments of the spinal cord through a number of very fine rootlets. According to classical knowledge, the cranial root gives motor innervation to the vocal cords, whereas the spinal root provides the motor innervation of the sternocleidomastoid muscle (SCM) and of the upper portions of the trapezius muscle (TZ). The specific function of each of the rootlets of the spinal component is not well known. Therefore the authors aimed to map, using intraoperative direct electrical stimulation and electromyographic (EMG) recordings, the innervation territory of these rootlets in relation to their exit level from the CNS. METHODS Forty-nine patients undergoing surgery with intradural exposure at the craniocervical junction were enrolled in the study. The EMG recordings included the sternal and clavicular parts of the SCM (SCM-S and SCM-C), the superior and middle parts of the TZ (TZ-S and TZ-M), and whenever possible the vocal cords. The main trunk of CN XI, its roots (both cranial and spinal), and when possible the fine cervical rootlets, were stimulated at predetermined locations, from the jugular foramen down to the lowest cervical level exposed. The EMG responses were collected, and a map of the responses was drawn up. RESULTS Monitoring and stimulation of the spinal root were performed in all cases, whereas for the cranial root this was possible in only 19 cases. A total of 262 stimulation sites were explored: 70 at the common trunk of the nerve, 19 at the cranial root, 136 at various levels on the spinal root, and 37 at the cervical rootlets. A vocal cord response was obtained by stimulation of the cranial root in 84.2% (16/19); absence of response was considered to have a technical origin. In no case did the vocal cords respond to the stimulation of the spinal root or rootlets. Stimulation of the cervical rootlets yielded responses that differed according to the level of stimulation: at C-1 the SCM-S responded 95.8% of the time (23/24); at C-2 the SCM-C responded 90.0% of the time (9/10); at C-3 the TZ-S responded 66.6% of the time (2/3); and below that level only the TZ-M responded. The spinal root stimulated at its various levels responded accordingly. CONCLUSIONS The function of each of the rootlets of CN XI appears to be specific. The cranial root contributes, independently of the spinal root, to the innervation of the vocal cords, which makes it a specific entity. The spinal root innervates the SCM and TZ with a cranio-caudal motor organization of its cervical rootlets.

Morphological characteristics of the cranial root of the accessory nerve.

There has been the controversy surrounding the cranial root (CR) of the accessory nerve. This study was performed to clarify the morphological characteristics of the CR in the cranial cavity. Fifty sides of 25 adult cadaver heads were used. The accessory nerve was easily distinguished from the vagus nerve by the dura mater in the jugular foramen in 80% of 50 specimens. The trunk of the accessory nerve from the spinal cord penetrated the dura mater at various distances before entering the jugular foramen. In 20% of the specimens there was no dural boundary. In these cases, the uppermost cranial rootlet of the accessory nerve could be identified by removing the dura mater around the jugular foramen where it joined to the trunk of the accessory nerve at the superior vagal ganglion. The cranial rootlet was formed by union of two to four short filaments emerging from the medulla oblongata (66%) and emerged single, without filament (34%), and usually joined the trunk of the accessory nerve directly before the jugular foramen. The mean number of rootlets of the CR was 4.9 (range 2-9) above the cervicomedullary junction. The CR of the accessory nerve was composed of two to nine rootlets, which were formed by the union of two to four short filaments and joined the spinal root of the accessory nerve. The CR is morphologically distinct from the vagus nerve, confirming its existence.

Distribution of the internal branch of the human accessory nerve.

It was recently reported that the internal branch of the accessory nerve not only comprises the cranial root but also various combinations of the cranial root, spinal root, and the vagal component of the vagus nerve. The aim of this study was to demonstrate the anatomical distribution of each component of the internal branch of the human accessory nerve. Ten half-heads and necks of adult cadavers were used. The internal branch of the accessory nerve had three courses: the pharyngeal branch, the descending branch to the thorax, and the recurrent laryngeal nerve. The pharyngeal branch of the internal branch originated mainly from the vagus nerve, rather than from the cranial root of the accessory nerve. All of the components of the internal branch descended to the thorax along the vagus nerve. The recurrent laryngeal nerve comprised the internal branch and the vagus nerve in all specimens, and it was separated into bundles originating from the internal branch and vagus nerve. Both bundles gave off branches to the trachea and esophagus. The laryngeal distribution of the internal branch and vagus nerve was confirmed in the posterior cricoarytenoid, lateral cricoarytenoid, and thyroarytenoid muscles. These three laryngeal muscles were innervated by the cranial root and/or vagus nerve, but the distribution pattern was different in each specimen. Although the vagus nerve and cranial root are morphologically distinct nerves in the cranial cavity, they can be regarded functionally as the same nerve based on their distribution in the laryngeal muscles.

Clinical anatomy of the cranial nerves

We are very happy to present this Special Issue on the cranial nerves to the readers of Clinical Anatomy. The history of the exploration of the cranial nerves and elucidation of their anatomy is ancient. Galen's classification of the cranial nerves (Table 1), notably excluding the olfactory nerves, was composed of seven pairs where it is interesting to note that the sixth pair included the glossopharyngeal, vagus and accessory nerves all travelling through the jugular foramen (Clarke and Jacyna, 1987). The cranial nerves were essentially identified, numbered and characterized based on the opening through which they exited the skull base. Our knowledge of the cranial nerves became more clearly discussed and disseminated by such medieval Middle Eastern and European scholars as Rhazes, Avicenna, Jorjani, Mundinus, Benedetti, Achillini, Massa and Berengario de Carpi (Shoja et al., 2007; Shaw, 1992). The Galenic seven-pair classification of the cranial nerves remained unchanged for more than a millennium until the celebrated German physician and anatomist, Samuel Thomas von Sömmerring, in 1778, implemented a novel classification scheme that is still used today (Squire et al., 2013). Niccolo Massa, an Italian physician and anatomist, was probably the first anatomist in Europe who challenged Galen's classification scheme by enumerating the olfactory nerves as the first pair of cranial nerves. Thomas Willis is notable for his work enumerating and illustrating nine cranial nerve pairs, including the olfactory nerves as the first pair and counting the trochlear, trigeminal and abducens nerves individually (Casey, 2007; Shaw, 1992). In this special issue of Clinical Anatomy, we have attempted to include a wide range of relevant articles with emphasis on their originality and clinical applications of the cranial nerves. The review article by Dr. Vilensky on cranial nerve 0 or the “neglected cranial nerve” is very informative. The special issue contains a landmark study by Dr. Tubbs and his colleagues, which represents “the largest study to date documenting the presence of a cranial root of the accessory nerve.” An article by Dr. Hendrix and colleagues (2014) on the arterial supply of the lower cranial nerves is one that needs specific mention. Skull base surgeons are often perplexed by the fact that following resection of a vestibular schwannoma, some patients develop facial nerve paralysis without their facial nerve being traumatized during the operation. The vast and complex anatomy of the cranial nerve blood supply may provide an explanation for this observation. Whether a proportion of patients with facial paralysis following tumor resection suffer from acute ischemic neuropathy secondary to arterial disruption needs further research. The first step in such research is to elucidate the anatomy of the arterial supply. The two articles on the anastomoses between lower cranial and upper cervical nerves (see Shoja et al., 2014a, 2014b) are products of an over three year review, which attempted to further elucidate the anatomy of the neural network formed by the lower cranial and upper cervical nerves and their branches. The reviews conclude that these nerves “with their extra-axial communications can be collectively considered a plexus.” The anatomy of this craniocevical nerve plexus needs to be revisited and appreciated in the anatomical literature. Ultimately, we hope that clinical anatomists from around the world will enjoy reading this issue and find its contents valuable in their teaching and research.

Variable composition of the internal and external branches of the accessory nerve

The purpose of this study was to clarify the composition of the internal and external branches (IB and EB) of the accessory nerve. Fifty-seven half heads of 34 adult cadavers were used. The IB and EB of the accessory nerve were mixed with the cranial root (CR), vagus nerve, and spinal root (SR). The IB was classified into five types and the EB into four types according to their composition. The IB consisted of only CR in 7.0% of the 57 cases, and of the CR and the vagus nerve in 52.6%; the IB did not exist in 12.3%. The EB was only composed of the SR in 19.3% of cases, the SR and CR in 52.6%, and the SR, CR, and the vagus nerve in 21.1%. There were 14 combinations of IB and EB types. The most common combination was the IB with the CR and the vagus nerve, and the EB with the SR and CR (31.6%). The combination of IB and EB comprising CR and SR, respectively, was not observed. The IB and EB are known to consist of the CR and SR of the accessory nerve, respectively. However, this study shows that there are no IB and EB comprising only the CR and SR, respectively, and the branches have various combinations of the CR, SR, and vagus nerve.

A Unique Case of Intradural Communicating Branches between the Accessory Nerve and the Dorsal Roots of the Cervical Spinal Nerves

The accessory nerve has cranial and spinal roots. The cranial roots emerge from the medulla, whereas the spinal roots arise from motor cells within the ventral horn of C1-C7 segments of the spinal cord. Communications have been described between the spinal accessory nerve rootlets and the dorsal rootlets of cervical spinal nerves. In the present case, we report a communication that has not been reported before and discuss the functional anatomy. During the dissection of the craniovertebral junction of a 67-year-old formalin-fixed adult male cadaver, a connection between the spinal accessory nerve rootlets and the dorsal rootlets of the cervical spinal nerves was observed. A communication between the spinal rootlets of the accessory nerve and the dorsal roots of cervical spinal nerves was present on the right and left side. On the right, a communication between the accessory nerve spinal rootlet and the dorsal rootlet of the fourth cervical spinal nerve existed. On the left, there were two branches from the lowest accessory nerve spinal rootlet, one run ventrally and the other dorsally to the spinal rootlet and reached the dorsal root of third cervical spinal nerve. The dorsal root of C1 did not exist on either the right or the left side. Further, an unusual spinal accessory nerve formation was also observed. This case does not fit into any of the previously described classifications in the literature. Therefore, the different variations concerning the communications between the spinal rootlets of the accessory nerve and the cervical spinal nerves should be kept in mind during both surgical, especially radical neck dissections, and nonsurgical evaluations.

Impaired cognition and hemispatial neglect in a woman with neck pain

MRI brain (Fig. 1A-C Images in Neuroscience: Question) revealed multiple subcentimeter gadolinium-enhancing foci throughout the leptomeninges and cortex. Cerebrospinal fluid (CSF) analysis revealed pleomorphic lymphocytosis with a low CSF/blood glucose concentration ratio (0.2, normal range > 0.6). Although infective processes, including tuberculosis (TB) are possible, the suspicious lesion behind the left ventricle (Fig. 1D Images in Neuroscience: Question) made cerebralmetastases from lung cancer themost likely diagnosis. Cerebral metastases from haematological dissemination usually results in a single or few nodules, which typically seed to the grey– white matter junction and are surrounded by oedema. This case is unusual, as there are numerous nodules throughout the leptomeninges and cortex andnoevidence of perilesional oedemaormass effect. Such ‘‘miliary’’metastatic tumoursor carcinomatousencephalitis are rare and usually present in patients with known systemic disease. Carcinomatous meningitis occurs in 5% of systemic malignancies and should be suspected in patients with aseptic meningitis, especially when underlying lung, breast or gastrointestinal tumours are present. Here, it is difficult to determine whether tumour cells spread from the brain parenchyma to the CSF or visa versa. Once in the subarachnoid space, however, dissemination to multiple meningeal sites overlying the brain and spinal cord is inevitable and there may be spread to the underlying parenchyma. Carcinomatous meningoencephalitis is characterized by cranial or spinal root neuropathies due to leptomeningeal disease in combination with focal neurological deficits or altered mental state attributable to cortical disease. Compression of cranial nerves as they exit the brainstem frequently presents as ophthalmoplegia or facial weakness, while aqueductal obstruction may result in hydrocephalus. Spinal root involvement presents as neck or back pain associated with compressive radiculopathies. Cortical involvement results in headache or altered mental state and disruption of the blood–brain barrier typically manifests as focal deficits, seizures or encephalopathy. In leptomeningeal disease CT scans are usually unremarkable and calcification or microhaemorrhage of cortical nodules is

Cranial roots of the accessory nerve exist in the majority of adult humans

The inclusion of a cranial root as a component of the accessory nerve is controversial with at least one recent study claiming that intracranial rootlets do not exist in humans. In response to this debate, the present study aimed to clarify this anatomy in a large cadaveric sample. In this study, 43 adult cadavers (86 sides) were dissected via a posterior approach to the craniocervical junction. Observations were made for the presence or absence of cranial roots of the accessory nerve, and when present, their lengths and diameters were measured. Relationships of these rootlets were documented. A cranial root of the accessory nerve was identified in 76% of sides. When identified, 1-6 cranial rootlets (mean 4.5) of the accessory nerve were observed. They ranged in diameter from 0.1 to 1.1 mm (mean 0.7 mm). The length of these nerves ranged from 8 to 24 mm with a mean of 17 mm. In general, the more superior rootlets were shorter and the more inferior rootlets were longer. Although there was a slight tendency for the cranial roots to be more numerous and larger on right sides and in males, this did not reach statistical significance. We believe this to be the largest study to date documenting the presence of a cranial root of the accessory nerve. Based on our findings, a cranial root exists in the majority of specimens. Neurosurgical procedures or high quality imaging of this area should enable the physician to see these structures.

Revision Surgery of the Lower Cranial Nerves Root

Revision Surgery of the Lower Cranial Nerves Root

Neurolymphomatosis: A Case Series of Clinical Manifestations, Treatments, and Outcomes (P04.187)

Objective: Our goal was to ascertain common factors to render earlier diagnosis, and prognostic factors to predict response to therapy. Background Neurolymphomatosis involves infiltration of malignant lymphocytes into the peripheral nervous system, specifically cranial nerves, roots, plexuses, and/or peripheral nerves. It is distinct from more common neurological complications related to chemotherapy, irradiation, paraneoplastic disorders, and leptomeningeal carcinomatosis. Design/Methods: We review five patients who developed neurolymphomatosis at M.D. Anderson Cancer Center between 2010 and 2011. Clinical, radiologic, and laboratory data were extracted from their medical records. Results: The average age at onset was 48 (range 26 - 76) with primary diagnosis being non-Hodgkin9s lymphoma in three (Burkitt9s, large B-cell) and leukemia in two (AML, CML). Initial symptoms included weakness (5/5), pain (3/5), and sensory change (2/5) and localized to lower extremities (3/5), upper extremities (2/5), unilateral (4/5), bilateral (1/5), and cranial nerve (1/5). Physical exam findings included weakness (5/5), sensory disturbance (5/5), atrophy (4/5), hypotonia (2/5), and hyporeflexia (5/5). Three patients demonstrated MRI abnormalities with clinical correlation, affecting neural foramina (1/5), paraspinal (2/5), or subcutaneous (1/5) regions; no patients had imaging evidence of parenchymal, spinal cord, or leptomeningeal pathology. All patients had positive EMG/NCS and diagnoses included mononeuritis multiplex, multifocal plexopathy, demyelinating polyneuropathy, and chronic axonal polyradiculoneuropathy. One patient had positive CSF cytology; PET was performed and positive in four patients and no nerve biopsies or autopsies were performed. Therapies included systemic (5/5) and intrathecal chemotherapy (4/5), immunomodulators (2/5), and plasma exchange (1/5); no patients underwent radiotherapy. Mortality was 40% with average survival from neurologic presentation 6 months (range 1–12 months); the other patients progressed despite treatment. Neither age, gender, malignancy type, recurrence, positive CSF/imaging/EMG, nor intervention correlated with worse prognosis. Conclusions: Further studies are warranted to define risk for developing neurolymphomatosis and identify factors affecting outcome. Disclosure: Dr. Gildersleeve has nothing to disclose. Dr. Hormozdi has nothing to disclose. Dr. Kamiya Matsuoka has nothing to disclose. Dr. Woodman has nothing to disclose.

CNS-Resident Glial Progenitor/Stem Cells Produce Schwann Cells as well as Oligodendrocytes during Repair of CNS Demyelination

After central nervous system (CNS) demyelination-such as occurs during multiple sclerosis-there is often spontaneous regeneration of myelin sheaths, mainly by oligodendrocytes but also by Schwann cells. The origins of the remyelinating cells have not previously been established. We have used Cre-lox fate mapping in transgenic mice to show that PDGFRA/NG2-expressing glia, a distributed population of stem/progenitor cells in the adult CNS, produce the remyelinating oligodendrocytes and almost all of the Schwann cells in chemically induced demyelinated lesions. In contrast, the great majority of reactive astrocytes in the vicinity of the lesions are derived from preexisting FGFR3-expressing cells, likely to be astrocytes. These data resolve a long-running debate about the origins of the main players in CNS remyelination and reveal a surprising capacity of CNS precursors to generate Schwann cells, which normally develop from the embryonic neural crest and are restricted to the peripheral nervous system.

Does herpes zoster ophthalmicus increase the risk of stroke?

Varicella zoster virus (VZV), a ubiquitous human herpesvirus, causes chicken pox on primary infection and then establishes lifelong latency in all cranial nerve, dorsal root, and autonomic ganglia. When VZV-specific cell-mediated immunity declines, such as in elderly and immunocompromised individuals, virus reactivates in one or more ganglia and typically travels peripherally to cause herpes zoster in the corresponding dermatomes. Herpes zoster can be complicated by stroke and has been described clinically as VZV vasculopathy, granulomatous angiitis, post varicella arteriopathy, and herpes zoster ophthalmicus (HZO) with delayed contralateral hemiparesis. The likely mechanism for stroke caused by VZV is direct viral infection of cerebral arteries. This assertion is supported by animal studies identifying afferent fibers from trigeminal and dorsal root ganglia to both intracranial and extracranial blood vessels, providing an anatomic pathway for spread of the virus,1,2 and observations of viral particles, antigens, and DNA in affected arterial vessels in VZV vasculopathy cases.3,4 Several studies have examined varicella and the risk of stroke in children,5,6 but large studies in the adult population regarding the frequency and risk of …

Math1 Is Essential for the Development of Hindbrain Neurons Critical for Perinatal Breathing

Mice lacking the proneural transcription factor Math1 (Atoh1) lack multiple neurons of the proprioceptive and arousal systems and die shortly after birth from an apparent inability to initiate respiration. We sought to determine whether Math1 was necessary for the development of hindbrain nuclei involved in respiratory rhythm generation, such as the parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN), defects in which are associated with congenital central hypoventilation syndrome (CCHS). We generated a Math1-GFP fusion allele to trace the development of Math1-expressing pFRG/RTN and paratrigeminal neurons and found that loss of Math1 did indeed disrupt their migration and differentiation. We also identified Math1-dependent neurons and their projections near the pre-Bötzinger complex, a structure critical for respiratory rhythmogenesis, and found that glutamatergic modulation reestablished a rhythm in the absence of Math1. This study identifies Math1-dependent neurons that are critical for perinatal breathing that may link proprioception and arousal with respiration.

Neuromuscular Specializations within Human Pharyngeal Constrictor Muscles

At present it is believed that the pharyngeal constrictor (PC) muscles are innervated by the vagus (X) nerve and are homogeneous in muscle fiber content. This study tested the hypothesis that adult human PCs are divided into 2 distinct and specialized layers: a slow inner layer (SIL), innervated by the glossopharyngeal (IX) nerve, and a fast outer layer (FOL), innervated by nerve X. Eight normal adult human pharynges (16 sides) obtained from autopsies were studied to determine 1) their gross motor innervation by use of Sihler's stain; 2) their terminal axonal branching by use of acetylcholinesterase (AChE) and silver stain; and 3) their myosin heavy chain (MHC) expression in PC muscle fibers by use of immunocytochemical and immunoblotting techniques. In addition, the specialized nature of the 2 PC layers was also studied in developmental (newborn, neonate, and senescent humans), pathological (adult humans with idiopathic Parkinson's disease [IPD]), and comparative (nonhuman primate [adult macaque monkey]) specimens. When nerves IX and X were traced from their cranial roots to their intramuscular termination in Sihler's-stained specimens, it was seen that nerve IX supplied the SIL, whereas branches of nerve X innervated the FOL in the adult human PCs. Use of AChE and silver stain confirmed that nerve IX branches supplying the SIL contained motor axons and innervated motor end plates. In addition to distinct motor innervation, the SIL contained muscle fibers expressing slow-tonic and alpha-cardiac MHC isoforms, whereas the FOL contained muscle fibers expressing developmental MHC isoforms. In contrast, the FOL became obscured in the elderly and in the adult humans with IPD because of an increased proportion of slow muscle fibers. Notably, distinct muscle fiber layers were not found in the human newborn and nonhuman primate (monkey), but were identified in the 2-year-old human. Human PCs appear to be organized into functional fiber layers, as indicated by distinct motor innervation and specialized muscle fibers. The SIL appears to be a specialized layer unique to normal humans. The presence of the highly specialized slow-tonic and alpha-cardiac MHC isoforms, together with their absence in human newborns and nonhuman primates, suggests that the specialization of the SIL maybe related to speech and respiration. This specialization may reflect the sustained contraction needed in humans to maintain stiffness of the pharyngeal walls during respiration and to shape the walls for speech articulation. In contrast, the FOL is adapted for rapid movement as seen during swallowing. Senescent humans and patients with IPD are known to be susceptible to dysphagia; and this susceptibility may be related to the observed shift in muscle fiber content.

Is the cranial accessory nerve really a portion of the accessory nerve? Anatomy of the cranial nerves in the jugular foramen

The accessory nerve is traditionally described as having both spinal and cranial roots, with the spinal root originating from the upper cervical segments of the spinal cord and the cranial root originating from the dorsolateral surface of the medulla oblongata. The spinal rootlets and cranial rootlets converge either before entering the jugular foramen or within it. In a recent report, this conventional view has been challenged by finding no cranial contribution to the accessory nerve. The present study was undertaken to re-examine the accessory and vagus nerves within the cranium and jugular foramen, with particular emphasis on the components of the accessory nerve. These nerves were traced from their rootlets attaching to the spinal cord and the medulla and then through the jugular foramen. The jugular foramen was exposed by removing the dural covering and surrounding bone. A surgical dissecting microscope was used to trace the roots of the glossopharyngeal nerve (CN IX), vagus nerve (CN X) and accessory nerve (CN XI) before they entered the jugular foramen and during their travel through it. The present study demonstrates that the accessory nerve exists in two forms within the cranial cavity. In the majority of cases (11 of 12), CN XI originated from the spinal cord with no distinct contribution from the medulla. However, in one of 12 cases, a small but distinct connection was seen between the vagus and the spinal accessory nerves within the jugular foramen.