Manikum Moodley

Investigation of NRXN1 deletions: clinical and molecular characterization.

Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility for autism and schizophrenia, and similar deletions have been identified in individuals with developmental delay and dysmorphic features. We have identified 34 probands with exonic NRXN1 deletions following referral for clinical microarray‐based comparative genomic hybridization. To more firmly establish the full phenotypic spectrum associated with exonic NRXN1 deletions, we report the clinical features of 27 individuals with NRXN1 deletions, who represent 23 of these 34 families. The frequency of exonic NRXN1 deletions among our postnatally diagnosed patients (0.11%) is significantly higher than the frequency among reported controls (0.02%; P = 6.08 × 10−7), supporting a role for these deletions in the development of abnormal phenotypes. Generally, most individuals with NRXN1 exonic deletions have developmental delay (particularly speech), abnormal behaviors, and mild dysmorphic features. In our cohort, autism spectrum disorders were diagnosed in 43% (10/23), and 16% (4/25) had epilepsy. The presence of NRXN1 deletions in normal parents and siblings suggests reduced penetrance and/or variable expressivity, which may be influenced by genetic, environmental, and/or stochastic factors. The pathogenicity of these deletions may also be affected by the location of the deletion within the gene. Counseling should appropriately represent this spectrum of possibilities when discussing recurrence risks or expectations for a child found to have a deletion in NRXN1.

Identifying and managing intracranial complications of sinusitis in children: a retrospective series.

Background: Of patients admitted to hospital with sinusitis, about 3% have an intracranial complication. We describe the clinical features, laboratory data, imaging findings, and outcomes of pediatric patients with intracranial complications of sinusitis. Methods: A retrospective chart review of all pediatric patients <21 years of age admitted for intracranial complications of sinusitis to a tertiary hospital over a 10-year period. Results: A total of 13 patients with a mean age of 13.3 ± 3.7 years presented with headache (92%), fever (85%), nausea/vomiting (62%), sinus tenderness (31%), and lethargy (23%). Physical examination findings included Pott puffy tumor (46%), orbital cellulitis (46%), altered level of consciousness (46%), new-onset seizure (31%), hemiparesis (23%), nuchal rigidity (23%), visual disturbance (23%), and slurred speech (15%). Computed tomography and magnetic resonance imaging demonstrated 16 instances of epidural and subdural empyema, and 1 brain abscess. One child had sagittal sinus thrombosis. Conclusions: Our findings suggest that acute sinusitis in combination with severe intractable headache, varying degrees of altered level of consciousness, focal neurologic deficits, and/or signs of meningeal irritation should raise clinical suspicion for potential intracranial complications of sinusitis. These signs and symptoms should prompt early and aggressive evaluation and management, including neuroimaging studies, neurologic and otolaryngologic consultations, and intravenous antibiotics.

Clinical Approach to Syncope in Children

Pediatric syncope is one of the most common neurological problems in the pediatric population in both the office setting and in the emergency department. The abrupt brief loss of consciousness is usually dramatic and alarming to patients, family, onlookers, and providers. The differential diagnosis of syncope is wide but most cases are benign. A comprehensive but focused history and a thorough clinical examination are usually the cornerstones in the diagnosis of high-risk patients. It should be noted that the evaluation of syncope in children is costly and testing provides a low diagnostic yield. This chapter reviews the various types of syncope and provides a succinct clinical approach to the diagnosis, investigation, and management of syncope in children.

A clinical picture of Guillain-Barré syndrome in children in the United States.

The authors describe the demographics, clinical presentation, investigation, treatment, and outcomes of pediatric patients with Guillain-Barré syndrome. They identified 35 pediatric patients with Guillain-Barré syndrome presenting to a tertiary academic center over a 20-year period. The most common presenting symptoms were paresthesias (54%), weakness (49%), and myalgias (49%). Sensation was affected in 54% of patients, and hyporeflexia or areflexia was present in 94% of patients. Cranial nerve dysfunction (46%) and autonomic involvement (eg, changes in blood pressure, pulse, bowel/bladder control, or priapism; 46%) were also common. Autonomic dysfunction, cranial nerve involvement, and albuminocytological dissociation were significantly associated with a decreased time to nadir, the point when symptoms peaked (P = .015, .007, and .005, respectively). Although not statistically significant, treatment with plasmapheresis had a better success rate than intravenous immunoglobulin. The authors’ results will help to further delineate the clinical picture of Guillain-Barré syndrome in children and refine treatment strategies.

Hirayama Disease in Children From North America

Hirayama disease has been mainly reported from Asia; only a few cases are from the Western hemisphere, particularly North America. This is a retrospective chart review of patients < 18 years, diagnosed with Hirayama disease from a single center over 10 years. We diagnosed 6 children (4 boys), 15.1 ± 1.2 years of age. Symptom onset was 3 months to 3 years before presentation. All had unilateral or bilateral asymmetric distal upper extremity weakness without objective sensory loss. Oblique amyotrophy and cold paresis were noted in 5. On electromyography, acute-on-chronic denervation was most frequently noted in cervical-8 (C8) and thoracic-1 (T1) myotomes followed by cervical-7 (C7) myotome in both upper limbs, sparing C5–C6 myotomes. Cervical magnetic resonance imaging (MRI) was abnormal in 3. Symptoms progressed over a mean of 16.5 months. Treatment consisted of placement of cervical collar. Heightened awareness of this entity among pediatric neurologists in North America will lead to early diagnosis and intervention, avoiding unnecessary investigations.

Pediatric-Onset Multiple Sclerosis: A Single Center Study:

Pediatric-onset multiple sclerosis (POMS), once thought to be rare, is now being diagnosed in increasing numbers in children. Despite improvements to diagnostic criteria, the diagnosis and management of POMS remains challenging. The aim of this study is to retrospectively describe a growing POMS patient population seen at a single center over a 13 year period. Epidemiologic, clinical, neuroimaging, laboratory features and therapeutic management and outcome data were collected and analyzed. These data support associations between MS and environmental triggers such as obesity and vitamin D deficiency. Presenting symptoms, magnetic resonance imaging and laboratory findings were consistent with the existing literature; however, the prevalence of cortical lesions and abnormal saccadic pursuit is higher than other reports. Data also demonstrate a shift in practice from first- to second-line therapies over the observed period.

ZEB2 Gene Mutation and Duplication of 22q11.23 in Mowat-Wilson Syndrome

Mowat-Wilson syndrome is a recently delineated multiple congenital anomaly syndrome characterized by a distinctive facial appearance in association with intellectual disability, microcephaly, agenesis of the corpus callosum, seizures, congenital heart disease, Hirschsprung disease, short stature, and genitourinary anomalies. We report a 2-year-10-month-old white female with this syndrome caused by mutations in the ZEB2 gene, and in addition a duplication of the 22q11.23, a previously undocumented occurrence.

Cerebral venous sinus thrombosis in a child with iron-deficiency anemia

A 19-month-old boy was admitted with severe pallor and irritability. There was no history of infection, trauma or bleeding. His diet was predominantly milk-based. Investigations revealed low hemoglobin (3.4 g/dl), low iron and ferritin (11 lg/dl and 16.4 ng/ml, respectively) suggestive of iron-deficiency anemia (IDA). There was no leucocytosis. On examination, his hydration status was normal and there was no lymphadenopathy or hepatosplenomegaly. He received packed red blood cell (PRBC) transfusion. IDA was attributed to the exclusively milk-based diet. However, even after PRBC transfusion, he continued to be irritable and was noted to be rubbing his head. On neurological examination, he was fussy but there were no focal neurodeficits. CT of the head was concerning for superior sagittal sinus thrombosis; MRI of the brain and MR venography showed cerebral venous sinus thrombosis (CVST) without hemorrhage or infarct (Fig. 1a, b). Hypercoagulable workup showed elevated IgG anticardiolipin antibodies (45 GPL; normal 0–9 GPL) and thrombocytosis (551,000 /lL). Rest of the hypercoagulable work-up included normal IgM anticardiolipin antibodies, negative protein C and S, antithrombin III, and factor V Leiden mutation. He was heterozygous for prothrombin gene G20210A mutation also noted in his mother without any history of clothing. He was treated with oral iron and subcutaneous low-molecularweight heparin for CVST. His irritability improved over 2 weeks, and at 3-month follow-up, he was doing well with normal developmental milestones. MRI/MRV after 3 months showed residual non-occlusive thrombus of superior sagittal sinus (Fig. 2a, b). His hemoglobin was 11.6 g/dl with normal platelets and negative anticardiolipin antibodies. IDA has a peak prevalence of 4–8 % in children between 12 and 36 months of age in developed countries [1]. Iron deficiency in children has been implicated in developmental abnormalities, ischemic stroke, CVST, breath-holding episodes, and pseudotumor cerebri [2, 3]. The frequency of childhood stroke which includes both arterial ischemic stroke and CVST is 2–3 per 100,000 children/year in North America [4]. IDA has a tenfold increased risk for acute stroke in well toddlers [5]. CVST is more closely associated with IDA than arterial ischemic stroke [5]. Clinical manifestations of CVST in the setting of IDA include irritability, lethargy, vomiting, headache, and seizures with or without focal neurodeficits [3, 6]. Our patient had persistent irritability without focal neurodeficits. Associated infections can contribute to CVST in the setting of IDA [6]. Most common finding on hypercoagulable work-up is reactive thrombocytosis [3, 5, 6] also noted in our case. In addition, our patient had elevated IgG anticardiolipin antibodies at presentation (normalized after 3 months) and found to be heterozygous for prothrombin gene mutation. These factors might have contributed to the increased risk of CVST in the setting of IDA in our case. Anemia causing microcytosis and reduced red blood cell P. S. Ghosh (&) Neurology, Mayo clinic, 200 First Street SW Gu-801, 55905 Rochester, Minnesota, USA e-mail: ghosh.partha@mayo.edu

Pearls & Oy-sters: Osteoid osteoma of the scapula masquerading as neuralgic amyotrophy

A 7-year-old previously healthy right-handed boy presented to the pediatric neurology clinic with right arm and shoulder pain of 4 months duration. The pain was severe in nature, could last for an hour, at times woke him up from sleep, and was partially relieved with acetaminophen and ibuprofen. About 4 weeks prior to presentation, his parents noticed that his right upper arm was thinner than the left. The patient denied any sensory loss or weakness of the right arm or other limbs. There was no history of recent trauma or immunizations. His birth and developmental history were unremarkable and there was no family history of neuromuscular disorders. On clinical examination, his higher mental function and cranial nerves were normal. Motor system examination revealed atrophy of the right upper arm. There was no shoulder drooping, scapular winging, wasting of the forearm and hand, or fasciculations of the muscles. There was no local tenderness, redness, or swelling and range of motion of the shoulder joint was …

Reversible brainstem edema due to hypertensive encephalopathy in an 8-year-old girl.

The authors report an 8-year-old girl with refractory status epilepticus due to hypertensive encephalopathy, secondary to end-stage renal disease. Brain magnetic resonance imaging (MRI) in the acute phase showed striking hyperintensities in the brain stem and medial thalamus along with subtle cortical lesions. After successful control of hypertensive crisis and status epilepticus, the patient recovered to her baseline. Near total resolution of the lesions was noted on follow-up imaging performed 9 days later. Predominant brainstem involvement as a feature of posterior reversible encephalopathy syndrome due to hypertensive crisis is extremely rare in children and has not been well documented.