How I do it: Subtemporal transtentorial approach for cavernous malformation of the pons.

BACKGROUND: Removal of a pontine cavernous malformation requires sufficient exposure since any restriction on surgical freedom may lead to suboptimal visualization of the lesion, injury to the brainstem, and neurological catastrophe. METHODS: We describe and demonstrate the subtemporal transtentorial approach to a cavernous malformation of the upper pons, with emphasis on adequate surgical exposure while avoiding the need for extensive bone removal of the skull base. CONCLUSIONS: The meticulous technique is paramount to the successful removal of any brainstem cavernous malformation. Along with the surgical exposure, delicate handling of the malformation is demonstrated in the accompanying operative video.

The spectrum of brainstem malformations associated to mutations of the tubulin genes family: MRI and DTI analysis.

OBJECTIVES: To describe the spectrum of brainstem malformations associated to mutations in the tubulin genes taking advantage of magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). METHODS: Fifteen patients (six males; median age, 1.25 years; range, 1 month to 31 years) with mutations in the tubulin genes (TUBA1A = 8, TUBB2B = 4, TUBB3 = 3) studied with MRI and DTI were included in the study. Brain MR exams were reviewed to describe the malformative aspects of the brainstem. Malformations of the supratentorial brain and cerebellum were also recorded. Tractography was performed in seven selected cases. RESULTS: Fourteen patients (93%) showed complex malformations of the brainstem. Most common findings, apparent on anatomical MR sequences, were brainstem asymmetry (12 cases, 5 of which with a crossed pattern characterised by a hypertrophic right medulla oblongata and hypertrophic left pons), short and small pons on midline (10 cases) and anterior brainstem clefting (6 cases). DTI revealed abnormal transverse pontine fibres (13 cases), fusion of corticospinal tracts and medial lemnisci (9 cases) and a small decussation of the superior cerebellar peduncles (7 cases). CONCLUSIONS: Conventional/anatomical MRI and DTI reveal a complex pattern of brainstem malformations associated with tubulin genes mutations. KEY POINTS: • Brainstem malformations affect 93% patients with mutated tubulin genes • MRI shows homolateral and crossed brainstem asymmetries, clefts and pons hypoplasia • DTI demonstrates irregular representation of transverse pontine fibres and fusion of corticospinal tracts.

Is Asymmetry of the Pons Associated with Hand Function and Manual Ability after Arterial Ischemic Stroke in Children?

AIM: This study was designed to investigate how the asymmetry of the brain stem is related to hand function and manual ability after arterial ischemic stroke (AIS) diagnosed during childhood. METHOD: Patients diagnosed with AIS during childhood (> 5 years old, diagnosis > 2 years before recruitment) and typically developing peers were recruited by the Swiss Neuropediatric Stroke Registry. Brainstem cross-sectional areas of each side at the level of the pons were measured. Pinch and grip strength were measured with a dynamometer, quality of upper limb movement by the Melbourne Assessment 2 and manual ability by the ABILHAND-kids. An asymmetry index was calculated for all measures (except the ABILHAND-kids). Differences between groups and correlations were calculated using nonparametric statistics. RESULTS: Fourteen AIS survivors without hemiparesis, 10 AIS survivors with hemiparesis, and 47 typically developing peers were assessed. Patients with hemiparesis showed the highest brainstem asymmetry. There was a significant positive correlation between brainstem asymmetry, the asymmetry of strength and quality of upper limb movement, and a significant negative correlation between brainstem asymmetry and manual ability. INTERPRETATION: In pediatric AIS survivors, brainstem asymmetry can serve as an indirect measure of corticospinal tract integrity. It is significantly correlated with strength, quality of movement, and manual ability.

Isolated neonatal bilateral vocal cord paralysis revealing a unilateral medullary defect: a case report.

BACKGROUND: Congenital bilateral vocal cord paralysis is a rare occurrence. Approximately half the cases are associated with a major comorbidity, usually neurological, neuromuscular or malformative. CASE PRESENTATION: In a male newborn, respiratory distress syndrome and stridor were observed immediately following birth. The cause was bilateral vocal cord paralysis in the adducted position. Neuroradiological investigation revealed a unilateral discontinuity between the upper pons and the right medulla oblongata. Hypoplasia of the right posterior hemiarches of C1-C2 and the right exo-occipital bone was observed, as was a small clivus. MR angiography showed the absence of the distal right vertebral artery, with hypoplasia and parietal irregularities of the proximal segments. Respiratory autonomy was not obtained despite endoscopic laser cordotomy, corticosteroid therapy and nasal continuous positive airway pressure. The infant died at the age of 4 weeks after treatment was limited to comfort care. CONCLUSIONS: A medullary lesion is an exceptional cause of congenital bilateral vocal cord paralysis. The strictly unilateral neurological and vascular defect and the absence of associated intracranial or extracranial malformation make this clinical case unique and suggest a disruptive mechanism. This case also highlights the help provided by advanced neuroimaging techniques, i.e. fibre tracking using diffusion tensor imaging, in the decision-making process.

A de novo missense mutation in the inositol 1,4,5-triphosphate receptor type 1 gene causing severe pontine and cerebellar hypoplasia: Expanding the phenotype of ITPR1-related spinocerebellar ataxia's.

We report a de novo missense mutation (c.7649T>A) in the inositol, 1,4,5 triphosphate receptor type 1 (ITPR1) gene in a patient with severe pontocerebellar hypoplasia. The mutation results in an amino acid substitution of a highly conserved isoleucine by asparagine (p. I2550N) in the transmembrane domain. Mutations and deletions of the ITPR1 gene are associated with several types of autosomal dominant spinocerebellar ataxia, varying in age of onset and severity. Patients have signs of cerebellar ataxia and at most, a mild cerebellar atrophy on MRI. In contrast, the patient we report here has profound cerebellar and pontine hypoplasia. Our finding therefore further expands the spectrum of ITPR1-related ataxias. © 2016 Wiley Periodicals, Inc.

tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia.

Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.

Decision-making in classic trigeminal neuralgia concurrent with a pontine cavernous malformation: Causal or coincidental association?

Trigeminal neuralgia is classically associated with neurovascular compression of the trigeminal nerve, at the root entry zone (REZ). However, patients are occasionally affected by intra-axial involvement of trigeminal sensory fibers caused by demyelinating diseases, strokes and, rarely, pontine cavernous malformations. We discuss the management strategies and decision-making process in a 55-year-old patient, affected by trigeminal neuralgia with 2 potential causative mechanisms: a neurovascular conflict at the trigeminal REZ and an ipsilateral cavernous malformation at the pontine nucleus of the trigeminal nerve.

Two different manifestations of locked-in syndrome.

Locked-in syndrome (LIS) is an entity that usually occur a consequence of the lesion of ventral part of pons. Etiology of locked-in syndrome can be vascular and nonvascular origin. Locked-in syndrome usually occurs as a consequence of thrombosis of intermedial segment of basilar artery that induces bilateral infarction of the ventrobasal part of the pons. Additionally, LIS can be caused by trauma which often leads to posttraumatic thrombosis of basilar artery. The incidence of locked-in syndrome is still unknown. The basic clinical features of locked-in syndrome are: quadriplegia (a consequence of disruption of corticospinal pathways located in ventral part of pons), different stages of paralysis of mimic musculature, paralysis of pharynx, tongue and palate with mutism and anarthria. The patient can not move, but is conscious and can communicate only by eye movements. Two patients with locked-in syndrome were present in this article. In the first case, the patient had classic locked-in syndrome that was first described by Plum and Posner. Other patient had incomplete form of locket-in syndrome which was first described by Bauer. In these two patients locked-in syndrome occurred as a consequence of trauma. In the first patient locked-in syndrome was caused by direct contusion of ventral part of pons while in other patient locked-in syndrome was a consequence of posttraumatic thrombosis of vertebrobasilar artery. The introduction of anticoagulant therapy, besides the other measures of intensive therapy, has shown complete justification in the second patient. The gradual partial recovery of neurologic deficit has developed in the second patient without any additional complications.

A new clinical presentation associated with pontine clefting, hyperpigmentation and short stature in addition to craniofacial, cardiac and developmental anomalies.

We report on a 13-year-old girl who was the first child of nonconsanguineous parents, and who suffered from short stature accompanied with mental retardation, generalized hyperpigmentation of the skin and craniofacial findings. Her cardiological examination revealed atrial septal defect, mitral valve prolapsus and atrial septal aneurysm. Brain scans revealed dilatation of the third and lateral ventricles and a pontine cleft. Growth hormone (GH) deficiency was observed during the evaluation of GH/IGF-I axis. All the laboratory tests performed including metabolic screening, conventional karyotype and oligonucleotide array were normal. Mutation analysis of the C2ORF3 7 gene revealed no mutation. The clinical signs seen in this patient likely represent a new dysmorphological syndrome which has not been previously described.

Inferior pontine segmentation abnormality in a child with sensorineural deafness: DTI analysis of fiber tracts.

MRI/DTI data are presented in a child with sensoneurinal hearing loss and swallowing disorder. MRI/DTI revealed hypoplastic 8th cranial nerves and an inferior pontine segmentation abnormality. Color-coded FA-maps revealed diminished/absent fiber tracts within the affected brainstem segment. This report may add another small puzzle piece to the ongoing research on brainstem malformations.

Pontocerebellar hypoplasia type 6: A British case with PEHO-like features.

Six subtypes of autosomal recessive pontocerebellar hypoplasia (PCH) have been identified and the genetic basis of four of these (PCH1, PCH2, PCH4, and PCH6) is known. PCH6 is associated with cerebral atrophy and multiple but variable respiratory chain defects in muscle and has been reported in one consanguineous Sephardic Jewish family. It is caused by mutations in the RARS2 gene which encodes mitochondrial arginine-transfer RNA synthetase. Here we describe a female patient born to nonconsanguineous British parents. She presented in the neonatal period with increased respiratory rate, poor feeding and transiently elevated blood and CSF lactate levels. She went on to manifest profound developmental delay and severe microcephaly. Edema of the hands, feet, and face were suggestive of a PEHO-like condition (progressive encephalopathy, edema, hypsarrhythmia and optic atrophy), although optic atrophy and hypsarrhythmia were absent. Cranial MRI at age 14 months showed generalized cerebral atrophy, thinning of the pons and gross atrophy and flattening of the cerebellar hemispheres. Muscle biopsies on two occasions were normal with normal respiratory chain studies. Despite the absence of respiratory chain defects, the phenotype was felt to be consistent with PCH6 and indeed two novel pathogenic RARS2 mutations were identified. Ours is the second report of PCH6 due to RARS2 mutations and demonstrates that respiratory chain abnormalities are not obligatory, whereas some features of PEHO might be present.

Two cases of pontocerebellar hypoplasia: ethical and prenatal diagnostic dilemma.

We report the clinical characteristics and the outcome of two cases of pontocerebellar hypoplasia (PCH) in one family. The objective of this report is to describe the mode of presentation, discuss the clinical course, and address the dilemma of prenatal diagnosis and the prospects for genetic diagnosis for PCH. The first case is a 4-year-old boy in whom the diagnosis was made in the neonatal period. Despite extensive prenatal follow-up during the mother's subsequent pregnancy, prenatal diagnosis could not be made and a second affected child was born. Both siblings have severe developmental delay. The cases raise an important ethical dilemma about the most appropriate intervention if the mother of a child affected with PCH becomes pregnant. PCH is considered to have an autosomal-recessive mode of inheritance and a recurrence risk of 25% in each pregnancy. Until recently when genetic mutations in PCH types 2, 4, and 6 began to be identified, the lack of well-recognized genetic testing precluded experts from making clear recommendations. The best advice to these parents was difficult or elusive. With two children currently affected, should the parents terminate or continue with the latest pregnancy? Extensive monitoring with serial prenatal ultrasound failed in the previous pregnancy and resulted in the birth of the second affected child. It is evident that serial ultrasound scan may not be helpful in making the diagnosis prenatally. Therefore, other diagnostic modalities such as magnetic resonance imaging may be necessary and should be considered. With the identification of genetic basis or mutations in PCH types 2, 4, and 6 and possible development of commercial genetic testing for these types of PCH, reproductive decision or genetic testing during pregnancy should be recommended to affected families to enable informed choices.

Significance of the Cerebellopontine Cistern Cross-Sectional Area and Trigeminal Nerve Anatomy in Trigeminal Neuralgia: An Anatomical Study Using Magnetic Resonance Imaging.

AIM: To evaluate the relationship between trigeminal neuralgia (TN) and potential magnetic resonance imaging (MRI)-related measurements in patients with TN. MATERIAL AND METHODS: Retrospective analysis of 104 patients with TN was performed. MRI studies of 98 healthy controls were included in the study to compare the parameters with TN patients’ measurements. MRI measurements of cerebellopontine cistern (CPC) cross-sectional area, trigeminal-pontine angle (TPA) width, and trigeminal nerve cisternal segment length and thickness were assessed on both symptomatic and asymptomatic sides using 1.5T MRI with constructive interference in steady-state sequences. The images were interpreted by two radiologists blinded to the affected sides of the patients. RESULTS: There were significant differences between the symptomatic and asymptomatic sides in terms of mean trigeminal nerve length (8.8 ± 2.34 mm vs. 9.39 ± 2.29 mm; respectively, p=0.001) and thickness (20.9 ± 9.6 mm2 vs. 25 ± 9.98 mm2, respectively; p < 0.001). The median cerebellopontine cistern cross-sectional area was considerably lower on the symptomatic side compared with the asymptomatic side [201 mm2 (interquartile range=93) vs. 224.5 mm2 (interquartile range=77), respectively; p < 0.001]. There were no significant differences between the trigeminal-pontine angle width on either side (38.32 ± 10.38 vs. 38.78 ± 10.9, respectively; p=0.679). There were no statistically significant differences between the right and left sides regarding these parameters in the control group. CONCLUSION: Smaller CPC cross-sectional area, trigeminal nerve length, and trigeminal nerve thickness on MRI were demonstrated to commonly exist on the symptomatic side in patients with TN. We suggest that this narrow space may increase the risk of vascular compression on the nerve.

Pontine tegmental cap dysplasia: the severe end of the clinical spectrum.

Pontine tegmental cap dysplasia (PTCD) is a newly described hindbrain malformation with distinct neuroradiological findings. Only 12 cases of PTCD have been described so far, all sporadic. We report 2 further patients. Both children presented after birth with significant feeding problems due to impaired mouth opening (previously not reported) and sucking difficulties. Facial, cochlear, and glossopharyngeal nerves were involved resulting in bilateral sensory deafness and a significant swallowing disorder requiring a gastrostomy. In one patient the trigeminal sensory nerve was also involved causing severe bilateral corneal clouding with impaired vision. Both patients showed only minimal developmental progress since birth and had no speech production. Furthermore, they had vertebral and rib anomalies. The patients died at the age of 15 and 32 months, respectively, due to intercurrent infections. The majority of patients reported previously were affected less severely. The presented patients may represent the severe end of the spectrum.

Rhabdomyolysis in pontocerebellar hypoplasia type 2 (PCH-2).

Pontocerebellar hypoplasia type 2, an autosomal recessive neurodegeneration with prenatal onset, is characterised by progressive microcephaly and chorea/dystonia and has not previously been associated with muscular involvement. The gene associated with PCH-2 is unknown. An episode of rhabdomyolysis is reported in two non-related children with PCH-2, fatal in one, precipitated by intercurrent disease. Muscle biopsies in two other PCH-2 patients, and in one rhabdomyolysis patient whose biopsy antedated this complication showed areas of myofibrillar disruption or necrosis. Postmortem muscle sampled in another case without neuromuscular symptoms revealed focal necrosis, regenerating small fibres and upregulation of HLA-ABC. Random serum creatine kinase values in six other PCH-2 patients without clinical signs of neuromuscular involvement were increased in four. Collected data provide preliminary evidence of a subclinical myopathy associated with PCH-2.

A developmental classification of malformations of the brainstem.

OBJECTIVE: With advances in imaging and genetics, malformations of the brainstem are being more commonly identified. We describe and classify brainstem anomalies in 138 patients ascertained over a period of 10 years METHODS: Magnetic resonance imaging studies and, where available, clinical records of the patients were retrospectively reviewed. Malformations were segregated according to magnetic resonance findings and classified when possible by embryological mechanisms RESULTS: The most common location for anomalies was the pons, which was involved in 114 patients. The midbrain was involved in 45 patients, whereas the medulla was involved in 14. In 53 patients, more than 1 region was affected (all 3 regions in 6 patients, midbrain and pons in 39, and medulla and pons in 8). The malformations were divided into four groups: (1) malformations with abnormal brainstem segmentation, (2) malformations with segmental hypoplasia, (3) postsegmentation malformations, and (4) malformations associated with abnormal cortical organization INTERPRETATION: The malformations of the brainstem identified in this study were diverse and complex. This proposed classification organizes them into groupings based on known genetics and embryological events. Use of this system will help clinicians and scientists to better understand these disorders and, ultimately, to better counsel families of affected patients.

Pontine tegmental cap dysplasia: a novel brain malformation with a defect in axonal guidance.

Four unrelated children are described with an identical brainstem and cerebellar malformation on MRI. The key findings are: vermal hypoplasia, subtotal absence of middle cerebellar peduncles, flattened ventral pons, vaulted pontine tegmentum, molar tooth aspect of the pontomesencephalic junction and absent inferior olivary prominence. Peripheral hearing impairment is present in all. Variable findings are: horizontal gaze palsy (1/4), impaired swallowing (2/4), facial palsy (3/4), bilateral sensory trigeminal nerve involvement (1/4), ataxia (2/4). Bony vertebral anomalies are found in 3/4. Additional MR studies in one patient using diffusion tensor imaging (DTI) with colour coding and fibre tracking revealed an ectopic transverse fibre bundle at the site of the pontine tegmentum and complete absence of transverse fibres in the ventral pons. The combined findings indicate an embryonic defect in axonal growth and guidance. Phenotypic analogy to mice with homozygous inactivation of Ntn1 encoding the secreted axonal guidance protein netrin1, or Dcc encoding its receptor Deleted in Colorectal Cancer led us to perform sequence analysis of NTN1 and DCC in all the patients. No pathogenic mutations were found. For the purpose of description the name 'pontine tegmental cap dysplasia' (PTCD) is proposed for the present malformation, referring to its most distinguishing feature on routine MRI.

Pontocerebellar hypoplasia type 1.

Pontocerebellar hypoplasias are heterogeneous disorders that share a reduction in the size of brainstem and cerebellum. We describe a patient with features of the rare combination of pontocerebellar hypoplasia and spinal motor neuron disease. Parental consanguinity, low Apgar scores, facial weakness, dysphagia, tongue fasciculations, stridor, generalized hypotonia, severe muscle weakness, areflexia, and congenital joint contractures were evident. Cranial magnetic resonance imaging revealed a small cerebellum and brainstem, and a muscle biopsy revealed neurogenic changes. These abnormalities suggested pontocerebellar hypoplasia type 1.

Congenital ocular motor apraxia.

PURPOSE: Congenital ocular motor apraxia is a rare disease characterized by defective or absent voluntary and optically induced horizontal saccadic movements. Jerky head movements or thrusts on attempted lateral gaze are a compensatory sign. Most affected children have delayed motor and speech development. Cases associated with systemic diseases, neurologic maldevelopment, metabolic deficits, and chromosomal abnormalities have been described. METHODS: Case report and review of the scientific literature. RESULTS: The authors describe the ophthalmologic, pediatric, and neurologic evaluations and follow up of a child with impaired horizontal saccades, jerky head movements, and delayed motor and speech development. CONCLUSIONS: Congenital ocular motor apraxia is an uncommon disorder of ocular motility. Even so, ophthalmologists should be aware of the developmental delay and the other associated conditions, in order to grant the patients the multidisciplinary assistance they often require.

Pontocerebellar hypoplasia type 2: variability in clinical and imaging findings.

We report 24 children (14 girls) who presented with the typical neuroimaging findings of pontocerebellar hypoplasia (PCH) to describe the clinical spectrum of type 2. Twenty-one presented with the classical form described by Barth; characteristic features (15/21) were breathing and/or sucking problems during neonatal period and early onset hyperkinetic movement disorder. Eighteen were normocephalic at birth, but all developed microcephaly during infancy. Development was severely affected with none of the children being capable of sitting, walking, or talking. Social contact and visual fixation were persistently poor. Dyskinetic movement disorder was present in all, in some together with mild spasticity. Seizures occurred in 14 (in 7 as neonates). Eight children died (age 1 day-6 years). Neuroimaging showed an absent or severely flattened pons, different degrees of vermian hypoplasia, with cerebellar hemispheres (wing-like structures) being equally or more affected. Three (all girls) were less severely affected clinically and did not develop the dyskinetic movement disorder, motor and cognitive development were somewhat better. Microcephaly was also a prominent sign. Severity of pontocerebellar neuroimaging findings did not differentiate between the typical and atypical clinical group and did not correlate with clinical outcome.