Congenital Cranial Dysinnervation Disorder: An Unusual Phenotype With Multiple Cranial Neuropathies and Novel Neuroimaging Findings.

Congenital cranial dysinnervation disorders result from a maldevelopment of brainstem nuclei and/or cranial nerves. In some cases, specific genetic abnormalities have been identified. We expand the clinical phenotype of these disorders with the report of a 28-month-old girl who was initially evaluated for seizures and was found to have right sixth nerve palsy, small optic discs with reduced vision in her right eye. Her development was delayed. Brain MRI showed multiple abnormalities involving other cranial nerves, the optic chiasm and brainstem. Her developmental delay and seizure disorder suggest additional cortical involvement.

CNTNAP1-Related Congenital Hypomyelinating Neuropathy.

BACKGROUND: Congenital hypomyelinating neuropathy is a rare form of hereditary peripheral neuropathy characterized by nonprogressive weakness, areflexia, hypotonia, severely reduced nerve conduction velocities, and hypomyelination. Mutations in contactin-associated protein 1 (CNTNAP1) were recently described as a cause of congenital hypomyelinating neuropathy. CNTNAP1-associated congenital hypomyelinating neuropathy is characterized by severe hypotonia, multiple distal joint contractures, and high mortality in the first few months of life. METHODS: Whole-exome sequencing was performed in two siblings with congenital hypotonia. Detailed phenotyping data were compared with previously reported cases. RESULTS: A novel, heterozygous compound mutation of CNTNAP1 was identified in both siblings. We also reviewed 17 patients harboring 10 distinct mutations from previously published studies. All patients presented with severe hypotonia, respiratory distress, and multiple cranial nerve palsies at birth. Six of 19 patients survived beyond infancy and required chronic mechanical ventilation. Seizures were common in the surviving patients. CONCLUSIONS: These findings suggest that CNTNAP1-related congenital hypomyelinating neuropathy is a distinct form of hereditary neuropathy that affects both the central and peripheral nervous systems with no clear phenotype-genotype correlation. Our findings also indicate that arthrogryposis multiplex congenita and early lethality are not universal outcomes for patients with congenital hypomyelinating neuropathy.

Isolated Congenital Absence of Cranial Nerves: Report of Two Cases.

Isolated cranial nerve absence is a rare condition that can be diagnosed using high-resolution cranial nerve magnetic resonance (MR) imaging. Thorough clinical examination with proper knowledge of the course of cranial nerves may help diagnose this rare condition. We describe two cases, one each of, isolated congenital absence of the third and seventh cranial nerve with their clinical presentation. High-resolution T2-weighted MR imaging was done in both patients which revealed absence of cisternal segment of the right-sided third nerve and cisternal with canalicular segment of the right-sided facial nerve.

Magnetic resonance imaging of developmental facial paresis: a spectrum of complex anomalies.

PURPOSE: Despite its clinical implications, the MRI features of developmental facial paresis (DFP) were described in a few case reports. This study aims to describe MRI features of DFP in relation to the embryological development with a proposed radiological new grading system. METHODS: The clinical records and MRI of the brain and internal auditory canal of 11 children with DFP were retrospectively reviewed. The following sequences were analyzed: axial, oblique sagittal SPACE of the internal auditory canal and brainstem; axial T2, T1WI and coronal T2WI of the brain. The severity of the maldevelopment of the seventh nerve was graded from 0 to 4: 0 = no abnormalities, 1 = unilateral facial nerve hypoplasia, 2 = unilateral facial nerve aplasia, 3 = aplasia or hypoplasia involving facial nerves on both sides, and 4 = facial nerve aplasia or hypoplasia associated with other cranial nerve palsy. RESULTS: Isolated facial nerve palsy was diagnosed in seven patients. It was of grade 1 in five and grade 3 in two. Hypoplasia of the nerve with interrupted course was encountered in two cases. Other associated cranial nerve abnormalities (grade 4) were seen in four patients; two of them were diagnosed previously as Moebius syndrome. In addition to inner ear anomalies, middle and external ear and parotid gland anomalies were described. CONCLUSION: To our knowledge, this is the largest series of patients with DFP that represents a continuum of isolated and combined malformations. Understanding of embryological basis can give insights into the anomalous development of the facial nerve.

The congenital cranial dysinnervation disorders.

Congenital cranial dysinnervation disorders (CCDD) encompass a number of related conditions and includes Duane syndrome, congenital fibrosis of the external ocular muscles, Möbius syndrome, congenital ptosis and hereditary congenital facial paresis. These are congenital disorders where the primary findings are non-progressive and are caused by developmental abnormalities of cranial nerves/nuclei with primary or secondary dysinnervation. Several CCDD genes have been found, which enhance our understanding of the mechanisms involved in brain stem development and axonal guidance.

Computed tomography is useful for preoperative identification of nonrecurrent laryngeal nerve in thyroid cancer patients.

OBJECTIVE: Nonrecurrent laryngeal nerve (NRLN) is a risk factor for nerve injury during thyroid or parathyroid surgery and is usually associated with vascular anomalies. This study investigated the usefulness of computed tomography (CT) scans for preoperative identification of NRLN in thyroid cancer patients. STUDY DESIGN: Case series with chart review. SETTING: Academic university hospital. SUBJECTS AND METHODS: Of the 6546 patients, 20 (0.3%) were intraoperatively identified with NRLN, and the medical records of 20 patients were reviewed retrospectively, with particular focus on preoperative CT findings. RESULTS: All 20 cases were right-sided NRLN, and no clinical symptoms were observed preoperatively in any patient. Two patients had type I NRLN and 18 had type II NRLN. NRLN injury occurred in 1 patient at a point where the nerve was close to the superior thyroid artery. Prior to surgery, surgeons identified only 5 suspected NRLN cases based on identification of vascular anomalies on CT scans. However, this review of CT scans revealed that vascular anomalies could be identified on the scans of all patients. CONCLUSIONS: Neck CT scanning appears to be an excellent method for predicting NRLN cases. However, thorough examination of the scans, with particular attention to the neck and mediastinum vascular structures, is required.

Congenital trigemino-abducens synkinesis in a neonate.

Congenital ocular synkinesis syndromes involve aberrant innervation of extraocular and eyelid muscles in a variety of patterns. A rare iteration is trigemino-abducens synkinesis, with only three published cases to date. Here the authors report (with video documentation) the earliest documented age of trigemino-abducens synkinesis and congenital ocular synkinesis in general. A 13-week-old (40-week postmenstrual age) girl presented with rhythmic abduction of the left eye that coordinated with sucking, likely resulting from abnormal embryologic development, causing activation of the lateral rectus by motor fibers of the mandibular branch of the trigeminal nerve.

Splitting of the extraocular horizontal rectus muscle in congenital cranial dysinnervation disorders.

PURPOSE: To analyze the horizontal rectus extraocular muscles (EOMs) by orbital magnetic resonance imaging (MRI) in patients with congenital cranial dysinnervation disorders that arises from abnormal development of cranial nerve nuclei or their axonal connections. DESIGN: Case series, retrospective analysis. METHODS: The morphology of the horizontal rectus EOMs was analyzed in orbital MRI on 4 patients with congenital oculomotor palsy, 26 with congenital superior oblique palsy, and five with Duane syndrome. Orbital imaging was performed by 1.5 tesla (T) and 3T MRI, and quasi-coronal and sagittal images perpendicular and parallel to the long axis of the orbit were obtained at slice thicknesses of 3 and 2 mm. RESULTS: The horizontal rectus EOMs were split in 4 of the 35 patients (11%). Splitting was observed in 2 of the five patients (40%) with Duane syndrome, one of the 26 patients (4%) with congenital superior oblique palsy, and 1 of the 4 patients (25%) with oculomotor palsy, but in none of the 6 normal subjects and 12 patients with acquired cranial nerve palsy. CONCLUSION: Since splitting of the horizontal rectus EOMs was noted in patients with congenital dysinnervation disorders, including Duane syndrome, Sevel's theory that the horizontal rectus EOMs develop from the superior and inferior mesodermal complexes is considered to be reasonable.

Quantitative analysis of electrically evoked auditory brainstem responses in implanted children with auditory neuropathy/dyssynchrony.

OBJECTIVE: Cochlear implantation is a common treatment approach for children with auditory neuropathy/dyssynchrony (AN/AD) who do not benefit from hearing aids. The auditory brainstem response (ABR) is a measure of neural synchrony along the auditory pathway up through the brainstem. By definition, acoustically evoked ABR is absent in AN/AD, however, ABR can be elicited by electrical stimulation through the cochlear implant (electrically evoked ABR [EABR]). Reports of EABR with AN/AD to date have been primarily descriptive in nature. The objective of this study was to quantify EABR wave V measures in implanted children with and without AN/AD. STUDY DESIGN: Retrospective analysis of EABR waveforms from March 2000 through February 2005. SETTING: Comprehensive Cochlear Implant Program/Tertiary Referral Center. PATIENTS: Pediatric cochlear implant users of two etiologic groups: congenital AN/AD (n = 5) and other congenital profound sensorineural hearing loss (n = 27). INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Intraoperative EABR wave V threshold, suprathreshold amplitude, and latency measures were compared between groups. RESULTS: The EABR threshold and suprathreshold amplitude measures across the population were variable regardless of etiology. With some exceptions, a trend was observed for the AN/AD group that included average or below-average thresholds and below-average suprathreshold response amplitudes. CONCLUSION: Cochlear implantation can provide synchronous neural responses to auditory stimulation in AN/AD, as previously known. The quantification of EABR measures in this study indicates that subjects with AN/AD have sufficient neural sensitivity to electrical stimulation, however, they may experience less robust neural responses at suprathreshold levels. Given the heterogeneity of potential causes of AN/AD, however, caution needs to be applied when grouping this population for analyses.

Imaging the cranial nerves: Part I: methodology, infectious and inflammatory, traumatic and congenital lesions.

Many disease processes manifest either primarily or secondarily by cranial nerve deficits. Neurologists, ENT surgeons, ophthalmologists and maxillo-facial surgeons are often confronted with patients with symptoms and signs of cranial nerve dysfunction. Seeking the cause of this dysfunction is a common indication for imaging. In recent decades we have witnessed an unprecedented improvement in imaging techniques, allowing direct visualization of increasingly small anatomic structures. The emergence of volumetric CT scanners, higher field MR scanners in clinical practice and higher resolution MR sequences has made a tremendous contribution to the development of cranial nerve imaging. The use of surface coils and parallel imaging allows sub-millimetric visualization of nerve branches and volumetric 3D imaging. Both with CT and MR, multiplanar and curved reconstructions can follow the entire course of a cranial nerve or branch, improving tremendously our diagnostic yield of neural pathology. This review article will focus on the contribution of current imaging techniques in the depiction of normal anatomy and on infectious and inflammatory, traumatic and congenital pathology affecting the cranial nerves. A detailed discussion of individual cranial nerves lesions is beyond the scope of this article.

Use of nerve growth factor to treat congenital neurotrophic corneal ulceration.

PURPOSE: This study was designed to assess the efficacy of nerve growth factor in the treatment of neurotrophic corneal ulceration in a child with bilateral congenital corneal anesthesia secondary to trigeminal insufficiency. METHODS: A 5-month-old child presented to the casualty department with a 2-week history of red eyes and right corneal ulceration. Slit-lamp examination showed a central defect in the right corneal epithelium with underlying stromal opacification, only mild conjunctival inflammation with slight decreased tear production, and otherwise apparently normal eyes. Initially this was investigated as an infected ulcer and treated for several weeks as herpetic ulceration with no beneficial effect. Further clinical examination demonstrated bilateral decreased corneal sensation along with decreased facial sensation in keeping with congenital trigeminal nerve insufficiency. Investigation with magnetic resonance imaging showed no obvious abnormality. Conservative treatment with lubricants resulted in progressive right corneal stromal loss, and no healing occurred in the left corneal ulcer. Bilateral large lateral tarsorrhaphies were performed. Despite this, the left corneal ulcer demonstrated no improvement and increasing stromal opacification was noted. Topical nerve growth factor (NGF) was then used to treat the left cornea and resulted in epithelial healing within 1 week. Treatment was continued for a further 10 days after epithelial healing. Despite conventional treatment on 3 separate occasions, further epithelial breakdown occurred. Topical NGF treatment resulted in a rapid improvement and healing of the epithelial defect.'At present, the patient is receiving a 6-month continuous treatment plan of NGF. RESULTS: Persistent epithelial defects (PED) secondary to neurotrophic ulceration have responded to topical NGF on 3 separate occasions during a 2-year period. The corneal epithelium now remains intact, and the cornea has no vascularization; however, mild anterior stromal opacification has gradually increased despite prolonged NGF treatment. CONCLUSION: NGF seems to represent a safe and efficacious treatment option to restore the integrity of corneal epithelium in which there is congenital corneal anesthesia because of trigeminal insufficiency. However, this treatment alone is insufficient to prevent progressive anterior stromal opacification.

[Speech disorders in Alajouanine syndrome]. / Zaburzenia mowy w zespole Alajouanine'a.

Alajouanine syndrome includes congenital, bilateral, central facial and abducens nerves palsy and clubfoot. The authors present speech disorders and helpful influence of early rehabilitation.

Clinical features of congenital absence of the superior oblique muscle as demonstrated by orbital imaging.

INTRODUCTION: Absence of an extraocular muscle was considered rare when demonstrable only by surgical exploration or necropsy. This study presents advances in orbital imaging to correlate clinical findings with absence of the superior oblique (SO) muscle. METHODS: We performed high-resolution coronal orbital imaging by magnetic resonance imaging (222 orbits) or computerized radiographic tomography (32 orbits) in 127 patients with strabismus. We reviewed the histories and ocular motility examinations in patients who had absence of 1 or both SO muscles. Findings were compared with patients who were clinically diagnosed with SO palsy but had demonstrable SO muscles on orbital imaging. RESULTS: SO muscles were absent in 6 patients. All had histories suggesting congenital strabismus. In patients old enough for quantitative testing who had unilateral SO muscle absence, visual acuity was a least 20/25 in all and stereopsis was better than 80 arc/s in one. Three patients were orthotropic in primary position. Five patients with unilateral SO muscle absence had clinical findings variably consistent with SO palsy, whereas a sixth patient with Duane syndrome had clinically unsuspected bilateral SO muscle absence. Versions and patterns of hypertropia in patients with SO muscle absence overlapped findings of 20 patients with SO palsy but demonstrable SO muscles. CONCLUSIONS: Imaging can frequently demonstrate absence of the SO muscle in patients with SO palsy. Such patients may have good vision and stereopsis and clinical findings indistinguishable from SO palsy without absence of the SO muscle. Orbital imaging should be considered in the evaluation of congenital SO palsy to facilitate planning of effective surgical correction.

Magnetic resonance imaging and tendon anomaly associated with congenital superior oblique palsy.

PURPOSE: To assess the relationship between tendon anomalies and the volume of the superior oblique muscle in patients with congenital unilateral superior oblique palsy. METHODS: Thirty-three patients with unilateral congenital superior oblique palsy were enrolled. Coronal, cross-sectional magnetic resonance imaging scans of the superior oblique muscle were obtained, and the volume of the paretic superior oblique muscle belly was calculated as a percentage of the superior oblique muscle belly on the normal side. The percentage volume of the affected superior oblique muscle was compared retrospectively with the angle of the vertical deviation in the primary position, the tendon looseness determined by a traction test, and other intraoperative findings. RESULTS: When a tendon was loose, the volume of its muscle belly was significantly smaller than the belly of muscles with a normal taut tendon (Mann-Whitney U test, P = .0005). The average vertical deviation of patients assessed to have loose tendons was 4.80 prism diopters, and the deviation in patients with normal tendons was 9.90 prism diopters. The mean vertical deviation of patients with atrophic muscle belly on magnetic resonance imaging was 18.1 prism diopters, and that with normal muscle structure was 10.1 prism diopters. The cases with loose tendon as determined by the traction test after administration of general anesthesia and the cases with atrophic muscle belly had significantly larger vertical deviation in the primary position than the cases with normal tendons and muscles. (Mann-Whitney U test, P = .01 and .0196, respectively). CONCLUSIONS: The traction test is sensitive enough to detect anomalies of the superior oblique tendons. Anomalous superior oblique tendons are nearly always associated with attenuated superior oblique muscle and this information provides us with an explanation for the phenomenon of laxity of the superior oblique tendon.

Möbius' syndrome: features and etiology.

PURPOSE: To review the clinical features and possible aetiology of all cases of Möbius' syndrome presented at the Royal Alexandra Hospital for Children in Sydney, Australia, from 1963 through 1995. METHODS: All charts of patients suffering from Möbius' syndrome were reviewed, and each patient was thoroughly assessed by a geneticist and a pediatric ophthalmologist. RESULTS: Patterns of systemic and ocular clinical features became evident. Of 23 patients in the series, 10 (43%) had a history significant events in utero. CONCLUSIONS: All patients suffering from Möbius' syndrome require thorough assessment by a multidisciplinary team including a geneticist or pediatrician and a pediatric ophthalmologist. Significant vascular events of pregnancy may explain some cases of fetal vascular disruption to the brainstem.

Physiological and perceptual features of dysarthria in Moebius syndrome: directions for treatment.

The functioning of the major subsystems of the speech production apparatus of a 12 year old female with Moebius syndrome was investigated using a battery of perceptual and physiological instrumental measures. Perceptual tests administered included: The Assessment of Intelligibility of Dysarthric Speech; the Frenchay Dysarthria Assessment; and a perceptual analysis of a speech sample based on a reading of the Grandfather Passage. Instrumental procedures included: spirometric and kinematic analysis of speech breathing; electroglottographic and aerodynamic evaluation of laryngeal function; nasometric assessment of velopharyngeal function; and evaluation of lip and tongue function using a variety of strain-gauge and pressure transducers. Consistent with the pathophysiological basis of Moebius syndrome, the major dysfunctions of the speech production mechanism were found at the level of the articulatory valve. Somewhat unexpectedly, however, impaired function was also identified at the level of the velopharyngeal and laryngeal valves by both the perceptual and instrumental assessments and at the level of the respiratory system by the physiological analysis alone. The results are discussed with reference to the neurological basis and clinical features of Moebius syndrome. The implications of the findings for the treatment of congenital dysarthria associated with Moebius syndrome are also discussed. The advantage of instrumental analysis over perceptual assessments in defining treatment goals for children with congenital dysarthria is highlighted.